STERIGMATOCYSTIN INDUCED ADENOCARCINOMA OF THE LUNG AND ATYPICAL HYPERPLASIA OF GLANDULAR STOMACH IN MICE

Aspergillus versicolor was isolated from the gastric juice of patients with chronic stomach diseases in high-risk area of gastric cancer. Mice fed with Aspergillus-inoculated corn flour developed adenocarcinoma of the lung in 15 of 35 mice (42.9%) and atypical hyperplasia of the glandular stomach in 13 of 35 mice (37.4%). Sterigmatocystin was identified by high performance liquid chromato-graphy (HPLC) and fluorescence spectrophotometry in the extract of Aspergillus-inoculated corn flour. The results suggest that the mycotoxin Sterigmatocystin may play a potential role in carcinogenesis in human.

THE EXPRESSION OF APOPTOSIS RELATED GENES IN THE PROCESS OF CANCERATION OF ATYPICAL HYPERPLASIA OF MAMMARY DUCT

Objective： To investigate the expression of apoptosis related genes p53 and bcl-2 in atypical hyperplasia of mammary duct and the relationship between the gene expression and oncogenesis of breast. Methods： mRNA of apoptosis related gene p53 and bcl-2 were detected by in situ hybridization in 44 cases of atypical ductal hyperplasia. p53 protein expression was detected by immunohistochemistry. The data were compared with those of 6 cases of benign hyperplasia and 26 cases of breast carcinoma. Results： The expression of p53 mRNA was 66.7% in benign hyperplasia, 40% in atypical ductal hyperplasia （55.6% in mild, 41.7% in medium, 26.1% in severe） and 19.2% in carcinoma （of which 21.4% were intraductal carcinoma and 16.7% were invasive）. The expression of p53 protein was negative in benign hyperplasia, 24% in atypical hyperplasia （mild 11.1%, medium 25%, severe 34.8%）, 38.5% in carcinoma （intraductal carcinoma 35.7%, invasive ductal carcinoma 41.7%）. The expression of bcl-2 was negative in benign hyperplasia, 78.6% in intraductal carcinoma, 83.3% in invasive ductal carcinoma. Conclusion： Loss and mutation of p53 gene and excessive expression bcl-2 mRNA were detected in severe atypical ductal hyperplasia.

Megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early-stage endometrial adenocarcinoma: a prospective study

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

Microscale endometrial sampling biopsy in detecting endometrial cancer and atypical hyperplasia in a population of 1551 women:a comparative study with hysteroscopic endometrial biopsy

Background:Endometrial cancer is one of the most common malignancies of the reproductive system.Effective and cost-effective screening method for populations at high risk is not available.This study aimed to investigate specimen adequacy and the influencing factors in microscale endometrial sampling biopsy and to evaluate the diagnostic accuracy and medical cost of biopsy in endometrial cancer and atypical hyperplasia screenings in comparison with hysteroscopic endometrial biopsy.Methods:A total of 1551 patients at high risk for endometrial lesions who required hysteroscopic endometrial biopsy from November 2017 to August 2018 were included.Microscale endometrial sampling biopsy was performed,followed by hysteroscopic endometrial biopsy.We evaluated the specimen adequacy and influencing factors of microscale endometrial sampling.Diagnostic consistency between microscale endometrial sampling biopsy and hysteroscopic endometrial biopsy was evaluated.The sensitivity,specificity,positive predictive value,and negative predictive value of microscale endometrial sampling biopsy in screening for endometrial cancer and atypical hyperplasia were analyzed,and the medical costs of the two procedures were compared.Results:The specimen adequacy was 81.2%.Patient age,menopausal status,endometrial thickness,and endometrial lesion type were correlated with specimen adequacy.There was good consistency in distinguishing benign and malignant endometrial diseases between microscale endometrial sampling biopsy and hysteroscopic biopsy(kappa 0.950,95%CI 0.925-0.975).The sensitivity,specificity,positive predictive value,and negative predictive value of microscale endometrial sampling biopsy were 91.7%,100.0%,100.0%,and 99.3%for endometrial cancer screening,respectively,and 82.0%,100.0%,100.0%,and 99.4%for atypical hyperplasia screening.The medical cost of endometrial sampling biopsy was only 22.1%of the cost of hysteroscopic biopsy.Conclusions:Microscale endometrial sampling biopsy is a minimally invasive alternative technique for obtaining adequate endometrial specimens for histopathological examination.It has the potential to be used in detecting endometrial cancer and atypical hyperplasia with high efficiency and low cost.

Expression of Survivin Gene among Human Normal Endometrium,Atypical Hyperplasia of Endometrium and Endometrial Carcinoma

Objective To investigate the expression of survivin gene among human normal endometrium,atypical hyperplasia of endometrium,and endometrial carcinoma.Methods Tissue samples of human normal endometrium during proliferative phase （NE,n=20）,atypical hyperplasia of endometrium （AHE,n=11）,and endometrial carcinoma （EC,n=9） were collected.Besides,Paraffin embedded sections of NE （n=20）,AHE （n=20）,and EC （n=20） were used.The expression of survivin gene was determined by immunohistochemistry and the real-time reverse transcription polymerase chain reaction.Results Survivin immunostaining appeared in the cytoplasm of endometrial epithelial cells.Both survivin staining and mRNA had higher levels in AHE or EC than those in NE （P〈0.01）.No difference was found on survivin staining and mRNA between AHE and EC （P〉0.05）.Conclusion High expression of survivin gene in human endometrium is associated with the risk of atypical hyperplasia progressing to endometrial carcinoma.The high level of survivin expression is useful as a predictive indicator for endometrial carcinoma.

Associations among benign prostate hypertrophy, atypical adenomatous hyperplasia and latent carcinoma of the prostate

Aim： To investigate the frequency of atypical adenomatous hyperplasia （AAH） and its associations with benign prostate hypertrophy （BPH） and latent histological carcinoma of the prostate （LPC） in autopsy material. Methods： Two hundred and twelve prostate specimens obtained from autopsy material were subjected to whole mount analysis in an attempt to investigate the associations among BPH, AAH and LPC. Results： Most histological carcinomas and AAH lesions were found in enlarged prostates with intense hypertrophy. No statistically significant relation was found between BPH and the main characteristics of LPC, such as tumor volume, histological differentiation and biological behavior. Our data regarding multi-focal tumors showed a tendency for multi-focal carcinomas to develop in larger prostates, and a tendency of AAH lesions to develop in larger prostates. No statistically significant relation was found between AAH and LPC. Conclusion： There seems not any causative aetiopathogenetical or topographical relation between AAH lesions and prostate adenocarcinoma. AAH lesion seems to be a well-defined mimicker of prostatic adenocarcinoma, and the reported association of AAH with prostatic carcinoma could probably be an epiphenomenon.

Atypical endometrial hyperplasia in a 35-year-old woman:A case report and literature review

BACKGROUND Atypical endometrial hyperplasia(AEH)is a common precancerous lesion of endometrial carcinoma(EC).The risk factors for AEH and EC directly or indirectly related to estrogen exposure include early menarche,nulliparity,polycystic ovarian syndrome,diabetes,and obesity.Both AEH and EC rarely occur in young patients(<40-years-old),who may desire to maintain their fertility.Evaluating the cancer risk of AEH patients is helpful for the determination of therapeutic plans.CASE SUMMARY We report a rare case of AEH in a 35-year-old woman who presented to the Hunan Provincial Maternal and Child Health Care Hospital with a large mass in the uterus.She married at 20-years-old,and had been married for more than 15 years to date.Several characteristics of this patient were observed,including nulliparity,limited sexual activity(intercourse 1-2 times a year)in recent years,and irregular vaginal bleeding for 2 years.Gynecological examination revealed an enlarged uterus,similar to the uterus size in the fourth month of pregnancy,and the uterine wall was relatively hard.Curettage was performed based on transvaginal sonography and magnetic resonance imaging results.Findings from the pathological examination were typical for AEH.The patient was cured after treatment with the standard therapy of high-dose progesterone.CONCLUSION In patients with intrauterine lumps that may be malignant,a pathological report should be obtained.

Preliminary Study on the Expression and the Significance of S-Phase Kinase Associated Protein 2 in Atypical Ductal Hyperplasia and Breast Cancer

OBJECTIVE To explore the relationship of high S-phase kinase associated protein 2 （Skp2） expression with the characteristics of breast cancer. METHODS Using a immunohistochemical method, Skp2 expression was detected and evaluated in 30 normal tissues, 30 atypical ductal hyperplasias （ADH）, 30 ductal carcinomas in situ （DCIS） and 56 invasive carcinomas （including invasive specific carcinoma and invasive nonspecific carcinoma）. The relationship between Skp2 expression and the characteristics of breast cancer was analyzed.RESULTS Skp2 expression varied among normal tissue, ADH, DCIS and invasive carcinomas （X^2=54.02, P〈0.005）. The positive level of Skp2 expression in DCIS was higher than that of normal tissue （X^2=21.82, P〈 0.005） and there was a significant difference in Skp2 between DCIS and ADH （X^2=5.08, P〈0.025） as well as between invasive carcinomas and DCIS （X^2=6.52, P〈0.01）. The positive expression level of Skp2 in invasive carcinomas with positive lymph nodes was remarkably higher compared to those with negative lymph nodes. A significant difference in Skp2 expression was found between combined histological Grades Ⅰ and Ⅱ versus Grade Ⅲ of invasive carcinomas （X^2=6.66, P〈0.01）. CONCLUSION High Skp2 expression may play an important role in carcinogenesis and biological behavior of breast cancer.

Reproductive advance of fertility preservation in patients with early endometrial carcinoma or endometrial atypical hyperplasia

Endometrial cancer(EC)is the fourth common cancer in women worldwide with its incidence rising each year.10%–15%young patients are diagnosed of EC.For patients of childbearing age with early endometrial cancer or atypical hyperplasia,it is necessary to consider surgical removal of uterus after they have given birth.It is a big challenge for reproductive doctors and oncologists to help such patients get pregnant safely as soon as possible.In this article,we will review the latest progress in conservative treatment and candidates for fertility preservation,application of molecular detection,the fertility outcome and follow-up treatment which aims to stimulate more thinking.

Atypical Ductal Hyperplasia of the Breast:Management of a Clinical Case at the IBN SINA Hospital Centre with Literature Review

Objective: To report a case of difficulties in the management of atypical ductal hyperplasia (ADH). Presentation of the case: Mrs. G, 50 years old, is consulting following the discovery at autopalpation of a lesion on her left breast. In its history: radical mastectomy Right Patey in 2004 for ductal carcinoma Infiltrant associated with carcinoma in situ;2 N+ /14;Positive hormone receptors. Adjuvant treatment performed: chemotherapy, radiotherapy and hormone therapy. Summary of the clinical case: Left breast examination: Superior External Quadrant nodule 5 cm × 4, mobile, hard, without inflammatory signs, there is no palpable lymph node. The surgical scar of the right breast is without particularity. Mammography and left breast ultrasound show an ACR4 lesion according to BIRADS. Microbiopsy: intradural papillomatous lesion requiring verification of the myoepithelial layer (P63 and CK5/6). Immunohistochemistry: atypical ductal hyperplasia (ADH) with no sign of transformation. Normal CA15-3 dosage. Treatment: broad surgical removal of the lesion. Analysis of the part shows a lesion with all the criteria of an HCA measuring 2 mm in its largest axis. The postoperative consequences are simple. Conclusion: The management of atypical hyperplasia is not consensual and is often undervalued. The type of lesion characterizing HCA is decisive for therapeutic orientation.

Endometrial carcinoma with cervical stromal invasion:Three case reports

BACKGROUND Endometrial cancer is a kind of well-known tumors of female genitourinary system.Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer.There is still controversy regarding the use of magnetic resonance imaging(MRI)in the diagnosis of cervical stromal invasion of endometrial cancer.The diagnosis of cervical stromal invasion varies significantly between different observers and institutions.We present a limited case series of the particular pattern of endometrial cancer,which infiltrates the cervical stroma and is often overlooked.CASE SUMMARY We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity.One patient,a reproductive-aged woman,exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage.A MRI scan revealed polypoid nodules within the internal cervical orifice.The other two cases were postmenopausal women who presented with abnormal vaginal bleeding.Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium.MRI scans did not detect any malignant signs in the endometrium.In one case,a nonthickened endometrium was observed,while in another,hyperplasia of the endometrium was seen.Notably,none of these patients had malignant tumors identified in the uterine cavity via MRI scans.However,postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion.CONCLUSION Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI.Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Effect of vinegar supplementation on patients with esophageal lesions lightly stained with Lugol’s iodine solution:Prospective single-centre trial

BACKGROUND Esophageal chromoendoscopy with iodine solution is important for detecting early esophageal cancer.The effect of routine treatment for lesions lightly stained with Lugol’s iodine solution is limited,and the addition of natural substances to a regular diet is becoming increasingly common.Vinegar has antitumor effects as reported in previous studies.AIM To evaluate whether vinegar supplementation could improve the prognosis of patients with lightly stained esophageal lesions.METHODSThis prospective single-centre trial included consecutive patients with lightly stained lesions between June 2020 and April 2022.Patients in the experimental group received increased amounts of vinegar for 6 months.The primary outcome of the study was the clinical therapeutic effect.Complications related to vinegar ingestion and adverse events were also recorded in detail.RESULTS A total of 166 patients were included in the final analysis.There was no significant difference in the baseline data between the two groups.Intention-to-treat(ITT)analysis demonstrated that the rates at which endoscopic characteristics improved were 33.72%in the experimental group and 20.00%in the conventional group(P=0.007);and the rates at which biopsy pathology improved were 19.77%and 8.75%,respectively(P=0.011).Additional vinegar consumption had a statistically protective effect on the rate at which endoscopic characteristics improved[hazard ratio(HR)_(ITT)=2.183,95%CI:1.183-4.028;HR_(per-protocol(PP))=2.307,95%CI:1.202-4.426]and biopsy pathology improved(HR_(ITT)=2.931,95%CI:1.212-7.089;HR_(PP)=3.320,95%CI:1.295-8.507).No statistically significant effect of increased vinegar consumption on preventing high-grade intraepithelial neoplasia or early cancer was observed(HR_(ITT)=0.382,95%CI:0.079-1.846;HRPP=0.382,95%CI:0.079-1.846).The subgroup analyses indicated that the overall therapeutic improvement of endoscopic characteristics and biopsy pathology seemed more obvious in older(age>60)male patients with small lesions(lesion size≤0.5 cm).Three patients in the experimental group reported acid regurgitation and heartburn.No adverse event during gastroscopy were recorded during follow-up.CONCLUSION A moderately increased ingestion of vinegar could not directly reduce the risk of esophageal cancer in the mucosa dysplasia population,but it improved the endoscopic characteristics and ameliorated the biopsy pathology to a certain extent.Further research is needed to verify the effect of nutritional intervention on precancerous esophageal lesions.

Expression and Clinical Significance of Vascular Endothelial Growth Factor in Benign and Malignant Tissues of Breast

Objective： To detect the expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） count in breast benign affection, breast atypical hyperplasia and breast carcinoma in situ, and to clarify the relationship between VEGF expression, MVD and the clinicopathological features of these diseases. Methods： The expression of VEGF and MVD count in 115 cases breast benign diseases （including 40 breast fibroid tumor, 40 breast cystic hyperplasia and 35 intraductal papilloma, 19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining （SP-method）. Results： The positive rate of VEGF in breast benign diseases, breast atypical hyperplasia and breast carcinoma in situ were 21.74%（25/115）, 31.58.% （6/19）and 53.13%（17/32） respectively. It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The expression of VEGF increased gradually in the three groups （P〈0.05）. The MVD count of the three groups were 14.41 ± 2.59, 18.89± 4.47 and 21.13 ± 4.12 respectively, It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The MVD count of the three groups increased gradually （P〈0.05）. In VEGF positive group, MVD count was 19.41 ±4.78; In VEGF negative group, MVD count was 14.91±3.15. The MVD count was higher in VEGF positive group than that in VEGF negative group （P〈0.05）. Conclusion： The results of this study suggested that VEGF could promote microvessel growth in breast tumors. The occurrence and progression of breast cancer might be related with the expression of VEGF.

Expressions of p16 and FHIT Proteins During Esophageal Carcinomatous Development in High Incidence Area of Esophageal Carcinoma

Objective： To detect the changes of p16 and FHIT and investigate their relationship in esophageal squamous cell carcinoma development by measuring their expression levels in normal squamous epithelium tissue, mild, moderate, severe dysplasia lesions, carcinoma in situ and invasive squamous cell carcinomas. Methods： Expressions of p16 protein and FHIT protein were detected and analyzed in 17 cases of normal squamous epithelium, 16 cases of mild dysplasia, 16 cases of moderate dysplasia, 17 cases of severe dysplasia, 10 cases of carcinoma in situ, and 18 cases of esophageal squamous cell carcinoma by immunohistochemical method. Results： With increasing histopathologic grades, the expressions of pl6 and FHIT became gradually lower. There was no remarkable difference of p16 and FHIT expressions between the normal and mild dysplasia group （P〉0.05）, but the differences between the normal and other groups were all significant （P〈0.05）. There was no remarkable difference among the squamous cell carcinoma group, the moderate and severe dysplasia groups, and the carcinoma in situ group （P〉0.05）, but significant differences existed in the expressions of p16 and FHIT proteins between the squamous cell carcinoma and the normal groups, and between the squamous cell carcinoma and the mild dysplasia groups （P〈0.05）. There was an association of descending trend between p16 and FHIT protein expressions. Conclusion： Reduced expressions of pl6 and/or FHIT proteins possible play an important role in the early occurrence of esophageal cancer. There was a positive correlation between the expressions of p16 and FHIT proteins.

Pregnancy outcomes after fertility preservation in women with endometrial carcinoma and atypical endometrial hyperplasia:A systematic review and meta-analysis

Objective:The objective of the study was to compare the effects of assisted reproductive technology(ART)and spontaneous pregnancy on pregnancy outcomes in women with endometrial carcinoma(EC)and atypical endometrial hyperplasia(AEH)following fertility-sparing treatments.Methods:Relevant studies published through July 2020 were identified from PubMed and Web of Science literature searches.The pregnancy outcomes of ART and spontaneous pregnancy were summarized and compared for women with complete remission of EC/AEH after fertility-sparing treatments.A subgroup analysis was performed based on whether patients had received in vitro fertilization and embryo transfer(IVF-ET)treatment.The complete remission and recurrence rates of EC/AEH following fertility-sparing treatments were estimated.The effect of pregnancy on recurrence rates of EC/AEH was also calculated.Results:Sixteen observational studies reporting pregnancy outcomes or recurrence with ART or spontaneous pregnancy for women with EC/AEH after fertility-sparing treatments were included.The complete remission rate of EC/AEH was 81.5%(95%CI,78%–85%).Compared with spontaneous pregnancy,the pregnancy rate of ART was significantly higher(66.8%vs.43.7%,OR=2.64,95%CI 1.71–4.05,P<0.00001,I^(2)=14%).Subgroup analysis showed that the pregnancy rate of IVF-ET was significantly higher than that of spontaneous pregnancy(62.7%vs.35.1%,OR=2.85,95%CI 1.44-5.63,P=0.003,I^(2)=29%).The live birth rate of ART was significantly higher than that of spontaneous pregnancy(75.3%vs.47.8%,OR=3.96,95%CI1.76-8.77,P=0.0009,I^(2)=45%).The recurrence rate of EC/AEH was 31%(95%CI 24%–39%).Clinical pregnancy could reduce the recurrence rate of EC/AEH,but there was no significant evidence of an association.Conclusions:ART,especially IVF-ET,could significantly improve pregnancy outcomes in women with EC/AEH receiving fertility-sparing treatments.Following complete remission,ART treatment might be a better option for women with EC/AEH than spontaneous pregnancy.

Clinicopathological Characteristics of Ten Patients with Atypical Glandular Hyperplasia Transformation of Adenomyosis

Although adenomyosis is a largely benign disease,malignant transformations do happen in rare cases,resulting in endometrioid adenocarcinoma or sarcoma in the myometrium.Recently, attention has been focused on the malignant transformation of the endometriosis.In 1988, the concept of atypical endometriosis （aEM） was first proposed by LaGrenade and Silverberg,[1] who suggested that aEM might be a precursor of malignant transformations of endometriosis.However, the majority of investigations of aEM focus on endometriosis, while adenomyosis remains understudied.In this article, we report 10 cases of atypical glandular hyperplasia transformation of adenomyosis, of whom the clinical and pathological characteristics are observed.

Analysis on Reverse of Atypical Endometrial Hyperplasia by Drugs in Patients with Polycystic Ovary Syndrome

Objective To analyze the efficacy and safety of drugs on reverse of atypical endometrial hyperplasia in patients with polycystic ovary syndrome （PCOS）. Methods Seventeen patients with PCOS complicated by atypical endometrial hyperplasia （9 patients who were treated with progestin but not reversed were considered as group A; 8 patients who were untreated were considered as group B） were retrospectively analyzed Both groups received oral glucose tolerance test （OGTT） and insulin release test, to check whether the patients had insulin resistance （IR） or hyperinsulinemia. The 17 patients were treated with oral contraceptives combined with metformin. Results After the 17 patients with PCOS complicated by IR and hyperinsulinemia received drug treatment for 3 -6 cycles, atypical endometrial hyperplasia was success- fully reversed Conclusion Oral contraceptives combined with metformin is a clinically practical and effective method for treatment of PCOS complicated by atypical insulin-resistant endometrial hyperplasia.

Low-Grade and High-Grade Invasive Ductal Carcinomas of the Breast Follow Divergent routes of Progression

Low-grade invasive ductal carcinoma is almost diploid, and has frequent losses of chromosome 16q, which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia （FEA）, atypical ductal hyperplasia （ADH）, and lownuclear grade ductal carcinoma in situ （DCIS）. The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma. This supports the linear progression model of breast cancer from FEA, through ADH, to low- nuclear grade DCIS as non-obligate early events in low-grade IDC evolution. In contrast, high-grade carcinoma tends to aneuploidy with complex genetic alterations--most importantly, frequent gains at chromosome 16q. Frequent losses at chromosome 16q in low-grade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process. Therefore, low-grade and high-grade IDC are two distinct diseases with a divergent route of progression.

C4.4A as a biomarker in pulmonary adenocarcinoma and squamous cell carcinoma

The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uP AR family of membrane proteins, qualifies as such a potential informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression to invasivecarcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A in squamous epithelium. In pulmonary adenocarcinomas, a fraction of cases is positive for C4.4A, which is surprising, given the origin of these carcinomas from mucin-producing and not squamous epithelium. Interestingly, this correlates with a highly compromised patient survival and a predominant solid tumor growth pattern. Circumstantial evidence suggests an inverse relationship between C4.4A and the tumor suppressor LKB1. This might provide a link to the prognostic impact of C4.4A in patients with adenocarcinomas of the lung and could potentially be exploited for predicting the efficacy of treatment targeting components of the LKB1 pathway.

Clinical features and outcome of 15 patients with recurrent endometrial cancer or atypical endometrial hyperplasia received primary fertility-sparing therapy followed by hysterectomy

Objective To investigate the clinical features and outcome of recurrent endometrial cancer(EC)or atypical endometrial hyperplasia(AEH)patients who underwent hysterectomy after fertility-sparing therapy.Methods Clinical data was retrospectively collected for 15 recurrent endometrial cancer or atypical endometrial hyperplasia patients who underwent hysterectomy in six hospitals from 2003 to 2019.According to the indicators of hysterectomy,patients were divided into four groups:7 patients who underwent direct hyesterectomy after the first relapse,4 due to re-treatment failure,1 after full term live birth,and 3 because of multiple recurrence.Clinical coexisting conditions,regimen and outcome of fertility-sparing therapy,pre-and post-operative pathological results,and prognosis were analyzed.Results(1)Fertility-spraring treatment was given to a total of 15 eligible patients,including 6 with EC and 9 with AEH.Median time interval from remission to recurrence was 12 months(range 3–92).Oral progestin-based medicine was the main fertility-sparing therapy in both primary treatment and re-treatment after recurrence.Six(6/8)patients received progestin combined with gonadotrophin releasing hormone agonist or metformin in three re-treatment groups.(2)Nine patients underwent hysterectomy and 6 staging surgery.Three patients had pathological upgrade after surgery.Five(5/10)EC patients had superficial myometrial invasion in postoperative pathology.All patients showed no evidence of disease in the median follow-up of 17 months(range 3–118).(3)Among seven patients who failed to re-treatment and had multiple recurrence,six were overweight/obesity and six had insulin resistance.Two of these patients had synchronous ovarian cancer in the postoperative pathology.Conclusion For the patients with recurrent EC or AEH after primary fertility-sparing therapy,overweight/obesity and insulin resistance might be the risk factors for re-treatment failure.Hysterectomy is recommended when patients had re-treatment failure or multiple recurrence;and generally the prognosis is favorable.