Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma

BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.

Clinicopathological features and trend changes of gastric carcinoma in Southern China

AIM: To investigate the clinicopathological features of gastric carcinoma in southern China and disease trends changes over the last 18 years.

Clinicopathological features of early gastric cancers arising in Helicobacter pylori uninfected patients

BACKGROUND Persistent Helicobacter pylori(H.pylori)infection causes chronic inflammation,atrophy of the gastric mucosa,and a high risk of developing gastric cancer.In recent years,awareness of eradication therapy has increased in Japan.As H.pylori infections decrease,the proportion of gastric cancers arising from H.pylori uninfected gastric mucosa will increase.The emergence of gastric cancer arising in H.pylori uninfected patients though rarely reported,is a concern to be addressed and needs elucidation of its clinicopathological features.AIM To evaluate the clinicopathological features of early gastric cancer in H.pyloriuninfected patients.METHODS A total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019.Of these,30 lesions in 30 patients were diagnosed as H.pylori-uninfected gastric cancer(Hp UIGC).We defined a patient as H.pylori-uninfected using the following three criteria:(1)The patient did not receive treatment for H.pylori,which was determined by investigating medical recordsand conducting patient interviews;(2)Lack of endoscopic atrophy;and(3)The patient was negative for H.pylori after being tested at least twice using various diagnostic methods,including serum anti-H.pylori-Ig G antibody,urease breath test,rapid urease test,and microscopic examination.RESULTS The frequency of Hp UIGC was 1.2%(30/2462)for the patients in our study.The study included 19 males and 11 females with a mean age of 59 years.The location of the stomach lesions was divided into three sections;upper third(U),middle third(M),lower third(L).Of the 30 lesions,15 were U,1 was M,and 14 were L.Morphologically,17 lesions were protruded and flat elevated type(0-I,0-IIa,0-IIa+IIc),and 13 lesions were flat and depressed type(0-IIb,0-IIc).The median tumor diameter was 8 mm(range 2-98 mm).Histological analysis revealed that22 lesions(73.3%)were differentiated type.The Hp UIGC lesions were classified into fundic gland type adenocarcinoma(7 cases),foveolar type welldifferentiated adenocarcinoma(8 cases),intestinal phenotype adenocarcinoma(7 cases),and pure signet-ring cell carcinoma(8 cases).Among 30 Hp UIGCs,24 lesions(80%)were limited to the mucosa;wherein,the remaining 6 lesions showed submucosal invasion.One of the submucosal invasive lesions showed more than 500μm invasion.The mucin phenotype analysis identified 7 Hp UIGC with intestinal phenotype and 23 with gastric phenotype.CONCLUSION We elucidated the clinicopathological characteristics of Hp UIGC,revealing recognition not only undifferentiated-type but also differentiated-type.In addition,intestinal phenotype tumors were also observed and could be an important tip.

Clinicopathological Features of Breast Cancer with Different Molecular Subtypes in Chinese Women

A retrospective study was performed to explore the relationship between molecular subtypes and clinicopathological features of breast cancer in Chinese women. Six hundred and twenty-eight Chi- nese women with breast cancer were classified into four molecular subtypes according to their estrogen receptor （ER）, progesterone receptor （PR） and Her-2 status. The prevalence rate of each molecular sub- type was analyzed. Relationship between the subtypes and clinicopathologic features was determined. The distribution of molecular subtypes was as follows： luminal A 46.5%, luminal B 17.0%, basal 21.5%, HER2/neu 15.0%. The subtypes had no significant difference under different menopausal status. How- ever, in the age-specific groups, the age group of〈35 years was more likely to get basal cell-like cancer （36.9%）. Statistically significant differences were found among molecular subtypes by age, nuclear grade, tumor size, lymph node （LN） metastasis, tumor stage by American Joint Committee on Cancer （AJCC）, radiotherapy but not by chemotherapy, types of surgery. After adjusting for several relative confounding factors, the basal subtype more likely had lower nodal involvement in both the incidence of LN metastasis （〉1 positive LN） and incidence of high-volume LN metastasis （〉4 positive LN）. The HER2/neu subtype had higher nodal involvement in the incidence of high-volume LN metastases. After adjusting for relative confounding factors, the HER2/neu subtype more likely had higher AJCC tumor stages. It was suggested that there existed close relationship between molecular subtypes and clinicopa- thological features of breast cancer. In addition, the breast cancer subtypes have been proven to be an independent predictor of LN involvement and AJCC tumor stage. These findings are very important for understanding the occurrence, development, prognosis and treatment of breast cancer in Chinese popu-lation.

Clinicopathological Features and Prognosis of Small Cell Carcinoma of the Cervix

Small cell carcinoma of cervix (SCCC) is a rare disease with highly aggressive behaviour and is pathologically hard to diagnose.In this study, the clinicopathological features, diagnosis, treatment and prognosis of the condition were examined.Clinical records and follow-up data of 7 cases of SCCC were retrospectively studied.Our results showed that five non-recurrent cases initially presented irregular vaginal bleeding or increased apocenosis of varying degrees.Pathological examination revealed that the stroma was diffusely infiltrated with small monomorphous cells ranging from round to oval shape.Three cases were immunohistochemically confirmed.One case was accompanied with squamous cell cancer.Of the 7 cases, one case was classified as stage Ⅰb 1, two stageⅠ b2, one stage Ⅱ a, one stage Ⅱb , and one stage Ⅲ b.On the basis of their stages of condition, one subject with stage III b underwent chemotherapy, and one with stage Ib2 received extensive hysterectomy plus pelvic lymphadenectomy, while the other 5 cases were treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre-and/or post-operative adjuvant chemotherapy and radiotherapy.Of the 7 patients, 4 had relapse-free survival of 14, 14, 16 and 28 months respectively.It is concluded that SCCC is an aggressive tumor with propensity for early pelvis lymph node metastases.Early-stage patients should be treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre-and/or post-operative adjuvant chemotherapy and radiotherapy.

Analysis of clinicopathological features and prognostic factors of breast cancer brain metastasis

BACKGROUND Breast cancer(BC)has become the most common malignancy in women.The incidence and detection rates of BC brain metastasis(BCBM)have increased with the progress of imaging,multidisciplinary treatment techniques and the extension of survival time of BC patients.BM seriously affects the quality of life and survival prognosis of BC patients.Therefore,clinical research on the clinicopathological features and prognostic factors of BCBM is valuable.By analyzing the clinicopathological parameters of BCBM patients,and assessing the risk factors and prognostic indicators,we can perform hierarchical diagnosis and treatment on the high-risk population of BCBM,and achieve clinical benefits of early diagnosis and treatment.AIM To explore the clinicopathological features and prognostic factors of BCBM,and provide references for diagnosis,treatment and management of BCBM.METHODS The clinicopathological data of 68 BCBM patients admitted to the Air Force Medical Center,Chinese People’s Liberation Army(formerly Air Force General Hospital)from 2000 to 2022 were collected.Another 136 BC patients without BM were matched at a ratio of 1:2 based on the age and site of onset for retrospective analysis.Categorical data were subjected to χ^(2) test or Fisher’s exact probability test,and the variables with P<0.05 in the univariate Cox proportional hazards model were incorporated into the multivariate model to identify high-risk factors and independent prognostic factors of BCBM,with a hazard ratio(HR)>1 suggesting poor prognostic factors.The survival time of patients was estimated by the Kaplan-Meier method,and overall survival was compared between groups by log-rank test.RESULTS Multivariate Cox regression analysis showed that patients with stage Ⅲ/Ⅳ tumor at initial diagnosis[HR:5.58,95% confidence interval(CI):1.99–15.68],lung metastasis(HR:24.18,95%CI:6.40-91.43),human epidermal growth factor receptor 2(HER2)-overexpressing BC and triple-negative BC were more prone to BM.As can be seen from the prognostic data,52 of the 68 BCBM patients had died by the end of follow-up,and the median time from diagnosis of BC to the occurrence of BM and from the occurrence of BM to death or last follow-up was 33.5 and 14 mo,respectively.It was confirmed by multivariate Cox regression analysis that patients with neurological symptoms(HR:1.923,95%CI:1.005-3.680),with bone metastasis(HR:2.011,95%CI:1.056-3.831),and BM of HER2-overexpressing and triple-negative BC had shorter survival time.CONCLUSION HER2-overexpressing,triple-negative BC,late tumor stage and lung metastasis are risk factors of BM.The presence of neurological symptoms,bone metastasis,and molecular type are influencing prognosis factors of BCBM.

Clinicopathological features of 11 cases of chronic hepatitis B infection complicated with primary biliary cholangitis

BACKGROUND Only a few cases of chronic hepatitis B(CHB)with primary biliary cholangitis(PBC)have been reported based on histological evidence from liver biopsies.AIM To observe the clinicopathological features and outcomes of 11 patients with CHB infection complicated by PBC.METHODS Eleven patients with CHB and PBC who underwent liver biopsy at the Zhenjiang Third Hospital,affiliated with Jiangsu University,and Wuxi Fifth People’s Hospital,from January 2005 to September 2020,were selected.All patients initially visited our hospital with CHB and were pathologically diagnosed with CHB and PBC.RESULTS Only five had elevated alkaline phosphatase levels,nine were positive for antimitochondrial antibody(AMA)-M2,and two were negative for AMA-M2.Two had jaundice and pruritus symptoms,10 had mildly abnormal liver function,and one had severely elevated bilirubin and liver enzyme levels.The pathological characteristics of CHB complicated by PBC overlapped with those of PBCautoimmune hepatitis(AIH).When necroinflammation of the portal area is not obvious,the pathological features of PBC are predominant,similar to the features of PBC alone.When the interface is severe,biliangitis will occur,with a large number of ductular reactions in zone 3.Unlike the PBC-AIH overlap pathology,this pathology is characterized by a small amount of plasma cell infiltration.Unlike PBC,lobulitis is often observed.CONCLUSION This is the first large case series to show that the rare pathological features of CHB with PBC are similar to those of PBC-AIH and small duct injury was observed.

Clinicopathological features of typical and nontypical hereditary non-polyposis colorectal cancer and their germline mutation of hMLH_1 and hMSH_2

Objective To study the clinicopathological features of the Chinese hereditary non-polyposis colorectal cancer and its germline mutation of hMLH1 and hMSH2. Methods Thirteen typical Chinese hereditary non-polyposis colorectal carcinoma (HNPC) C kindreds and 19 nontypical HNPCC families were registered and followed up. The germline mutation of the hMLH1 and hMSH2 of 12 index cases of 6 typical and 6 nontypical NHPCC were screened by PCR-SSCP. Samples with abnormal mobility were sequenced direcdy. Results The average age of typical HNPCC was 47, no difference existed between sexs. Location of the tumors of typical HNPCC represented 44.7% on the right half colon and non-typical HNPCC 65. 8% on the rectum. The rate of the metachronos cancer was 11.5%. The 3 - , 5 - and 10 -year survival rate was 64. 0%, 45. 3% and 31. 2% respectively. Among 12 cases, 8 showed abnormal mobility. Except for an intron polymorphinism, six exons abnormalities were found in 5 of 12 proband. Sequencing showed 4 missense,7

Clinicopathological features and prognosis of membranoproliferative-like Henoch-Schönlein purpura nephritis in children

Background: The aim of this retrospective study was to defi ne the clinical manifestations, pathological features and prognosis of children with membranoproliferative-like Henoch-Schönlein purpura nephritis (HSPN), representing International Study of Kidney Disease in Children (ISKDC) grade VI. Methods: Among 245 patients with HSPN treated in our hospital between 2008 and 2010, nine patients (3.7%) were diagnosed with HSPN of ISKDC grade VI (males=5, females=4, age: 9.5±2.03 years, mean±SD). The clinical features, laboratory and pathologicalfi ndings, treatment and outcome of the 9 patients were retrospectively analyzed. Results: Of the 9 patients, 7 (78%) presented with hematuria and nephrotic syndrome, and were treated with steroids (oral prednisone or intravenous methylprednisolone pulse therapy) and immunosuppressants (oral tripterygium glycosides or intravenous cyclophosphamide pulse therapy). One (11%) patient had hematuria and nephrotic range proteinuria (>50 mg/kg per 24 hours) and was treated with oral prednisone and tripterygium glycosides. Another (11%) patient presented with hematuria and moderate proteinuria (25-50 mg/kg per 24 hours) and was treated with oral tripterygium glycoside only. Histopathological examination showed diffuse glomerular mesangial and endocapillary proliferation, mesangial interposition, double-contour formation, podocyte hypertrophy, shedding, and cytoplasmic absorption droplets. The percentages of glomeruli with small cellular crescents varied from 4%-25% in 6 of 9 patients. Follow-up for 2 to 4 years showed excellent recovery in all patients. Conclusions: The main clinical feature of ISKDC grade VI HSPN in children is a nephrotic syndrome with hematuria. The excellent prognosis of the disease was probably related to early diagnosis and treatment with steroids and/or immunosuppressants, and mild degree of glomerulosclerosis and tubulointerstitial damage.

Clinicopathological analysis of small intestinal metastasis from extra-abdominal/extra-pelvic malignancy

BACKGROUND The metastatic tumors in the small intestine secondary to extra-abdominal/extrapelvic malignancy are extremely rare.However,the small intestine metastases are extremely prone to misdiagnosis and missed diagnosis due to the lack of specific clinical manifestations and examination methods,thus delaying its treatment.Therefore,in order to improve clinical diagnosis and treatment capabilities,it is necessary to summarize its clinical pathological characteristics and prognosis.AIM To summarize the clinicopathological characteristics of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy,and to improve the clinical capability of diagnosis and treatment for rare metastatic tumors in the small intestine.METHODS The clinical data of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy were retrieved and summarized,who admitted to and treated in the Air Force Medical Center,Chinese People’s Liberation Army.Then descriptive statistics were performed on the general conditions,primary tumors,secondary tumors in the small intestine,diagnosis and treatment processes,and prognosis.RESULTS Totally 11 patients(9 males and 2 females)were enrolled in this study,including 8 cases(72.3%)of primary lung cancer,1 case(9.1%)of malignant lymphoma of the thyroid,1 case(9.1%)of cutaneous malignant melanoma,and 1 case(9.1%)of testicular cancer.The median age at the diagnosis of primary tumors was 57.9 years old,the median age at the diagnosis of metastatic tumors in the small intestine was 58.81 years old,and the average duration from initial diagnosis of primary tumors to definite diagnosis of small intestinal metastases was 9 months(0-36 months).Moreover,small intestinal metastases was identified at the diagnosis of primary tumors in 4 cases.The small intestinal metastases were distributed in the jejunum and ileum,with such clinical manifestations as hematochezia(5,45.4%)and abdominal pain,vomiting and other obstruction(4,36.4%).In addition,2 patients had no obvious symptoms at the diagnosis of small intestinal metastases,and 5 patients underwent radical resection of small intestinal malignancies and recovered well after surgery.A total of 3 patients did not receive subsequent treatment due to advanced conditions.CONCLUSION Small intestinal metastases of extra-abdominal/extra-pelvic malignancy is rare with high malignancy and great difficulty in diagnosis and treatment.Clinically,patients with extra-abdominal/extra-pelvic malignancy should be alert to the occurrence of this disease,and their prognosis may be improved through active surgery combined with standard targeted therapy.

Clinicopathological Characteristics and Prognosis of Patients with Adenosquamous Lung Carcinoma

This study was aimed to characterize clinicopathological features and prognosis of patients with adenosquamous lung carcinoma（ASC）. Among the 2531 patients with lung cancer who underwent surgery between January 2000 and June 2012 in our hospital, 59 were histologically diagnosed as having ASC. The clinicopathological features and follow-up data of ASC patients were collected and analyzed statistically. Superior lobectomy was accomplished in 40 patients, middle and inferior lobectomy in 3, lobectomy plus partial resection of contralateral lung in 5, partial lung resection in 4, and pneumonectomy in 7. Moreover, 22 cases were found to be adenocarcinoma-predominant, and 18 to be squamous cell carcinoma-predominant. The median survival time was 13.6 months, and the 1-, 3-, and 5-year survival rates were 59.9%, 36.4% and 31.2%, respectively. Of the 52 cases with tissue specimens available, 11 had an EGFR mutation（21.2%） and 2 had a KRAS mutation（3.8%）. Multivariate analysis showed that histology subtype, pleural invasion, TNM stage, and postoperative treatment were all independent prognostic factors. The data from the current study demonstrated that SCC-predominant histology represents a better prognosis of ASC. Histology subtype, pleural invasion, TNM stage, and postoperative treatment are independent prognostic factors for ASC and adjuvant therapy may help control the disease.

Analysis of Clinicopathologic Features of Esophageal Carcinoma Patients Undergoing Surgery-a Report of 4,329 Cases

OBJECTIVE To investigate the clinicopathological features of esophageal carcinoma （EC） patients, and to analyze epidemiologic characteristics and the current situation of esophageal cancioma in the southern area of Hebei Province. METHODS A total of 4329 patients with esophageal cancinoma, undergoing surgery in the Fourth Hospital of Hebei Medical University during a period from January 1996 to December 2005, were selected. Collection and statistical analysis of the pathologic data were performed using a SAS 6.0 software package. RESULTS Over the past ten years, there has been a tendency for an increase in the mean age of EC onset （P 〈 0.05）, a downtrend in the percentage of squamous cancer （SqCa） （P 〈 0.05） and an uptrend in the frequency of small cell carcinoma （P 〈 0.05）. In clinical stages, there was a drop in the percentage of Stage-Ⅱ squamous EC patients （P 〈 0.05）, and an increase in that of Stage-Ⅳ patients （P 〈 0.05）. There were statistical differences in sex, age, pathologic types, depth of infiltration, ratio of stages and lymph node metastasis, etc. among the superior, middle and inferior segments of the EC diseased region （P 〈 0.05）. CONCLUSION It was relatively late for the EC patients from this area to see a doctor, resulting in a drop in the ratio of SqCa and an ascensus in that of small cell cancer. However, due to a low incidence of adenocarcinoma, no obvious ascending tendency was found in the frequency of this carcinoma over the past ten years.

Changing trends of clinicopathologic features and survival duration after surgery for gastric cancer in Northeast China

BACKGROUND Through analyzing the data from a single institution in Northeast China,this study revealed the possible clinicopathologic characteristics that influence the prognosis of patients with gastric cancer(GC).AIM To evaluate the changing trends of clinicopathologic features and survival duration after surgery in patients with GC in Northeast China,which is a highprevalence area of GC.METHODS The study analyzed the difference in clinicopathologic features and survival duration after surgery of 5887 patients who were histologically diagnosed with GC at the Harbin Medical University Cancer Hospital.The study mainly analyzed the data in three periods,2000 to 2004(Phase 1),2005 to 2009(Phase 2),and 2010 to 2014(Phase 3).RESULTS Over time,the postoperative survival rate significantly increased from 2000 to 2014.In the past 15 years,compared with Phases 1 and 2,the tumor size was smaller in Phase 3(P<0.001),but the proportion of high-medium differentiated tumors increased(P<0.001).The proportion of early GC gradually increased from 3.9%to 14.4%(P<0.001).A surprising improvement was observed in the mean number of retrieved lymph nodes,ranging from 11.4 to 27.5(P<0.001).The overall 5-year survival rate increased from 24%in Phase 1 to 43.8%in Phase 3.Through multivariate analysis,it was found that age,tumor size,histologic type,tumor-node-metastasis stage,depth of invasion,lymph node metastasis,surgical approach,local infiltration,radical extent,number of retrieved lymph nodes,and age group were independent risk factors that influenced the prognosis of patients with GC.CONCLUSION The clinical features of GC in Northeast China changed during the observation period.The increasing detection of early GC and more standardized surgical treatment effectively prolonged lifetimes.

Ultrasonographic and clinicopathologic features of benign Brenner tumors of the ovary

Objective The aim of this study was to summarize and analyze the ultrasonographic and clinicopathologic features of benign brenner tumors of the ovary.Methods Forty-six patients with brenner tumors of the ovary were included,and the imaging and pathologic features of the tumors were analyzed.Results Thirty-eight cases were unilateral,while eight cases were bilateral.The tumors were located only in the left ovary in 32 patients and in the right ovary in six patients.The median diameter of the tumors was 62 mm,and the diameter ranged from 15 to 270 mm.Vascular tumors were not observed.Most of the tumors(22/46)showed micro-perfusion,while 16 tumors showed no blood flow signal.Acoustic signal shadows after the cysts were observed in 26 tumors,accounting for 57%of all brenner tumors.Fourteen patients showed unilocular or multilocular tumors with no distinct characteristics on ultrasonography.Sixteen masses showed a multilocular solid structure,accompanied by calcification and a post-mass shadow;the solid structure showed mild-to-moderate vascularization on Doppler examination.Sixteen masses showed a pure solid structure,accompanied by calcification,resulting in an acoustic shadow behind the tumor;the solid structure showed mild-to-moderate vascularization on Doppler examination.Conclusion Some ultrasonographic features,including calcification with shadow,poor blood circulation of solid components,and mass localization,are helpful in the diagnosis of benign brenner tumors.

Somatic mutations in FAT cadherin family members constitute an underrecognized subtype of colorectal adenocarcinoma with unique clinicopathologic features

BACKGROUND The FAT cadherin family members(FAT1,FAT2,FAT3 and FAT4)are conserved tumor suppressors that are recurrently mutated in several types of human cancers,including colorectal carcinoma(CRC).AIM To characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members.METHODS We analyzed 526 CRC cases from The Cancer Genome Atlas PanCancer Atlas dataset.CRC samples were subclassified into 2 groups based on the presence or absence of somatic mutations in FAT1,FAT2,FAT3 and FAT4.Individual clinicopathological data were collected after digital slide review.Statistical analysis was performed using t tests and chi-square tests.RESULTS This CRC study cohort had frequent mutations in the FAT1(10.5%),FAT2(11.2%),FAT3(15.4%)and FAT4(23.4%)genes.Two hundred CRC patients(38.0%)harbored somatic mutations in one or more of the FAT family genes and were grouped into the FAT mutated CRC subtype.The FAT-mutated CRC subtype was more commonly located on the right side of the colon(51.0%)than in the rest of the cohort(30.1%,P<0.001).It showed favorable clinicopathologic features,including a lower rate of positive lymph nodes(pN1-2:33.5%vs 46.4%,P=0.005),a lower rate of metastasis to another site or organ(pM1:7.5%vs 16.3%,P=0.006),and a trend toward an early tumor stage(pT1-2:25.0%vs 18.7%,P=0.093).FAT somatic mutations were significantly enriched in microsatellite instability CRC(28.0%vs 2.1%,P<0.001).However,FAT somatic mutations in microsatellite stable CRC demonstrated similar clinicopathologic behaviors,as well as a trend of a better diseasefree survival rate(hazard ratio=0.539;95%confidence interval:0.301-0.967;log-rank P=0.073).CONCLUSION FAT cadherin family genes are frequently mutated in CRC,and their mutation profile defines a subtype of CRC with favorable clinicopathologic characteristics.

Prognostic factors of breast cancer brain metastasis

In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical Oncology.Brain metastasis is one of the most serious complications of breast cancer and causes high morbidity and mortality.Brain metastases may involve the brain parenchyma and/or leptomeninges.Symptomatic brain metastases develop in 10%-16%of newly recognized cases each year,and this rate increases to 30%in autopsy series.Depending on the size of the metastatic foci,it may be accompanied by extensive vasogenic edema or may occur as small tumor foci.Since brain metastases are a significant cause of morbidity and mortality,early diagnosis can have significant effects on survival and quality of life.The risk of developing brain metastases emerges progressively due to various patient and tumor characteristics.Patient variability may be particularly important in the susceptibility and distribution of brain metastases because malignant blood must cross the brain barrier and move within the brain parenchyma.Some characteristics of the tumor,such as gene expression,may increase the risk of brain metastasis.Clinical growth,tumor stage,tumor grade,growth receptor positivity,HER2 positivity,molecular subtype(such as triple negative status,luminal/nonluminal feature)increase the risk of developing breast cancer metastasis.Factors related to survival due to breast cancer brain metastasis include both tumor/patient characteristics and treatment characteristics,such as patient age,lung metastasis,surgery for brain metastasis,and HER2 positivity.If cases with a high risk of developing brain metastasis can be identified with the help of clinical procedures and artificial intelligence,survival and quality of life can be increased with early diagnosis and treatment.At the same time,it is important to predict the formation of this group in order to develop new treatment methods in cases with low survival expectancy with brain metastases.

Bridging the gap: Predicting brain metastasis in breast cancer

Chen et al explored clinicopathological features and prognostic factors,revealing advanced tumor stage,lung metastases,HER-2 overexpression,and triple-negative status as key contributors.Recent research connects astrocytes'role in brain metastasis with signaling pathways and the impact of Trastuzumab on HER-2 tumor survival.Factors such as positive HER2 status,lack of estrogen receptor expression,and liver metastasis are identified as additional risk factors.The routine use of magnetic resonance imaging,insights into gene mutations associated with metastasis,and the role of radiotherapy,including prophylaxis possibilities,is controversial in clinical practice.Understanding these risk factors in a multidisciplinary collaboration is precise for local treatments and targeted therapies,particularly for HER2+tumors,impacting directly on longer survival.

Characterization of E-cadherin expression in normal mucosa,dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis

BACKGROUND Gastric cardia adenocarcinoma(GCA),which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries,is of similar geographic distribution with esophageal squamous cell carcinoma in China,and even referred as"sister cancer"by Chinese oncologists.The molecular mechanism for GCA is largely unknown.Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers.However,the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis.AIM To characterize E-cadherin expression in normal gastric cardia mucosa,dysplasia and GCA tissues,and its influence on prognosis for GCA.METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases.The enrollment criteria included radical surgery for GCA,but without any radio-or chemo-therapy before operation.The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue(n=208)and dysplasia lesions(n=156)were collected,and processed as tissue microarray for immunohistochemistry.The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter,telephone or home interview.E-cadherin protein expression was determined by two step immunohistochemistry.Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients.RESULTS Of the 4561 GCA patients,there were 3607 males with a mean age of 61.6±8.8 and 954 females with a mean age of 61.9±8.6 years,respectively.With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA,the positive immunostaining rates for E-cadherin decreased significantly from 100%to 93.0%and 84.1%,respectively(R2=0.9948).Furthermore,E-cadherin positive immunostaining rate was significantly higher in patients at early stage(0 and I)than in those at late stage(II and III)(92.7%vs 83.7%,P=0.001).E-cadherin positive expression rate was significantly associated with degree of differentiation(P=0.001)and invasion depth(P<0.001).Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative(P=0.026).It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis.However,in patients with negative lymph node metastasis,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.036).Similarly,in patients with late stage GCA,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.011).CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

BACKGROUND Aberrant methylation in DNA regulatory regions could downregulate tumor suppressor genes without changing the sequences.However,our knowledge of secreted protein acidic and rich in cysteine(SPARC)and its aberrant methylation in gastric cancer(GC)is still inadequate.In the present research,we performed fundamental research to clarify the precise function of methylation on SPARC and its significance in GC.AIM To investigate promoter methylation and the effects of the SPARC gene in GC cells and tissues and to evaluate its clinical significance.METHODS Plasmids that overexpressed the SPARC gene were transfected into human GC BGC-823 cells;non-transfected cells were used as a control group(NC group).Quantitative real-time polymerase chain reaction and western blotting(WB)were then used to detect the expression of SPARC.Methylation-specific polymerase chain reaction was executed to analyze the gene promoter methylation status.Cell viability was measured by the cell counting kit-8 assay.The migration and invasion ability of cells were detected by scratch assays and transwell chamber assays,respectively.Cell cycle events and apoptosis were observed with a flow cytometer.RESULTS The expression of SPARC mRNA in GC tissues and cells was significantly lower and showed differing degrees of hypermethylation,respectively,than that in normal adjacent tissues and control cells.Treatment with 5-Aza-2’-deoxycytidine(5-Aza-Cdr)was able to restore the expression of SPARC and reverse promoter hypermethylation.Overexpression of the SPARC gene significantly inhibited proliferation,migration,and invasion of GC cells,while also causing cell cycle arrest and apoptosis;the NC group exhibited the opposite effects.CONCLUSION This study demonstrated that SPARC could function as a tumor suppressor and might be silenced by promoter hypermethylation.Furthermore,in GC cells,SPARC inhibited migration,invasion,and proliferation,caused cell cycle arrest at the G0/G1 phase,and promoted apoptosis.

Meta-analysis of immunohistochemical expression of hypoxia inducible factor-1α as a prognostic role in gastric cancer

AIM: To conduct a meta-analysis to evaluate the prognostic role of hypoxia inducible factor-1&#x003b1; (HIF-1&#x003b1;) expression in gastric cancer.