Ductal carcinoma in situ within a fibroadenoma:A case report and review of literature

BACKGROUND Fibroadenoma(FA)is the most common tumor found in young women,although it can occur in any age group.Ductal carcinoma in situ(DCIS)that is confined in a FA is rare;it is most frequently reported as an incidental finding.CASE SUMMARY We report a case of DCIS within a FA in a 46-year-old female without cancerrelated personal and family histories.The patient was diagnosed with a breast conglomerate of nodules and was followed for 1 year.In the current control image study,we found suspicious microcalcification,as a new finding,within one of the nodules.Consequently,a core biopsy of the tumor,which appeared hypoechoic,oval,and circumscribed,was performed.The pathological diagnosis was ductal carcinoma in situ within a fibroepithelial lesion.The patient underwent breastconserving surgery and received radiotherapy as well as endocrine therapy(tamoxifen).CONCLUSION We recommend a multidisciplinary approach for adequate treatment and followup.

Detection and Clinical Significance of Peripheral Blood CTC, CA125, CA153, and CEA Levels in Patients with Ductal Carcinoma in situ

Objective:To explore the detection and clinical significance of peripheral blood CTC,CA125,CA153,and CEA levels in patients with DCIS.Methods:210 patients who received surgical treatment for breast cancer in our hospital from January 2019 to December 2022 were selected as the research subjects.According to the postoperative pathology,100 cases were divided into breast cancer and 110 benign breast tumor groups.One hundred ten healthy patients undergoing physical examination during the same period were selected as the control group.CA153,CA125,and CEA levels were observed in the three groups.Results:The levels of CA153,CA125,and CEA in the breast cancer group were significantly higher than those in the benign breast tumor group and the control group(P<0.05);the levels of CA153,CA125,and CEA in the benign breast tumor group were all higher than those in the control group,but the differences were not statistically significant;among the three tumor markers,CA153 has the highest sensitivity at 39.00%,CA125 has the second highest sensitivity at 18.00%,and CEA has the lowest sensitivity at 17.00%;The sensitivity of the two joint tests of CA153+CA125,CA153+CEA,and CA125+CEA for the diagnosis of breast cancer were 50.00%,48.00%,and 26.00%respectively;the sensitivity of the three joint tests is the highest,reaching 53.00%,while the specificity of the joint tests was lower than the individual tests.Conclusion:Detection of peripheral blood CTC,CA125,CA153,and CEA levels has specific reference significance for the treatment and prognosis of DCIS patients.

Diffusion-tensor imaging as an adjunct to dynamic contrastenhanced MRI for improved accuracy of differential diagnosis between breast ductal carcinoma in situ and invasive breast carcinoma

Objective： To determine the value of diffusion-tensor imaging （DTI） as an adjunct to dynamic contrastenhanced magnetic resonance imaging （DCE-MRI） for improved accuracy of differential diagnosis between breast ductal carcinoma in situ （DCIS） and invasive breast carcinoma （IBC）. Methods： The MRI data of 63 patients pathologically confirmed as breast cancer were analyzed. The conventional MRI analysis metrics included enhancement style, initial enhancement characteristic, maximum slope of increase, time to peak, time signal intensity curve （TIC） pattern, and signal intensity on FS- T2WI. The values of apparent diffusion coefficient （ADC）, directionally-averaged mean diffusivity （D^vg）, exponential attenuation （EA）, fractional anisotropy （FA）, volume ratio （VR） and relative anisotropy （RA） were calculated and compared between DCIS and IBC. Multivariate logistic regression was used to identify independent factors for distinguishing IBC and DCIS. The diagnostic performance of the diagnosis equation was evaluated using the receiver operating characteristic （ROC） curve. The diagnostic efficacies of DCE- MRI, DWI and DTI were compared independently or combined. Results： EA value, lesion enhancement style and TIC pattern were identified as independent factor for differential diagnosis of IBC and DCIS. The combination diagnosis showed higher diagnostic efficacy than a single use of DCE-MRI （P=0.02）, and the area of the curve was improved from 0.84 （95% CI, 0.67-0.99） to 0.94 （95% CI, 0.85-1.00）. Conclusions： Quantitative DTI measurement as an adjunct to DCE-MRI could improve the diagnostic performance of differential diagnosis between DCIS and IBC compared to a single use of DCE-MRI.

Is sentinel lymph node biopsy necessary for the patients diagnosed with breast ductal carcinoma in situ using core needle biopsy or vacuum-assisted biopsy as the initial diagnostic method？

Axillary lymph node status is one of the most important prognostic indicator of survival for breast cancer, especially in ductal carcinoma in situ （DCIS）. The purpose of this study was to investigate whether sentinel lymph node biopsy （SLNB） should be performed in patients with an initial diagnosis of DCIS. Methods： A retrospective study was performed of 124 patients with an initial diagnosis of DCIS between March 2000 and June 2014. The patients were treated with either SLNB or axillary node dissection during the surgery, and we compared the clinicopathologic characteristics, image features, and immunohistochemical results. Results： Eighty-two patients （66.1%） had pure DCIS and 25 （20.2%） had DCIS with microinvasion （DCISM）, 17 （13.7%） updated to invasive breast cancer （IBC）. 115 patients （92.7%） underwent SLNB, among them, 70 patients （56.5%） underwent axillary node dissection. 3 of 115 patients （2.6%） had a positive sentinel lymph node, only 1 （1.4%） of 70 patients had axillary lymph node metastasis, in 84 patients （66.7%） who were diagnosed DCIS by core needle biopsy （CNB） and vacuum-assisted biopsy （VAB）. 26 patients （31.0%） were upstaged into IBC or DCISM in the final histological diagnosis. The statistically significant factors predictive of underestimation were large tumor size, microcalcifications, comedo necrosis, positive Her-2 status, negative estrogen receptor status. Conclusion： The metastasis of sentinel lymph nodes in pure DCIS is very low, but the underestimation of invasive carcinoma in patients with an initial diagnosis of DCIS is an usual incident, especially in the cases when DCIS is diagnosed by CNB or VAB. Our findings suggest patients presenting with a preoperative diagnosis of DCIS associated with large tumor sizes, microcalcifications, comedo necrosis, positive Her-2 status, negative ER status are more likely to be DCISM and IBC in final diagnosis. SLNB should be performed in this part of patients.

Preoperational diagnosis and management of breast ductal carcinoma in situ arising within fibroadenoma:Two case reports

BACKGROUND Ductal carcinoma in situ(DCIS)arising within fibroadenoma is a type of tumor that is rarely encountered in clinic,with only about 100 cases of carcinoma arising within a fibroadenoma reported in the literature.Here,we present two cases of breast DCIS arising within a fibroadenoma and discuss their clinical and imaging findings as well as treatment.CASE SUMMARY The patients did not have cancer-related personal and family histories.Case 1(a 49-year-old woman)was diagnosed with a bilateral breast nodule in May 2018 and was followed(preoperative imaging data including ultrasound and mammography)for 3 years;she underwent an excisional biopsy to address an enlargement in nodule size.Case 2(a 37-year-old woman)was diagnosed with a left breast nodule in June 2021 and consequently received vacuum-assisted biopsy of the tumor which appeared as“irregularly shaped”and“unevenly textured”tissue on ultrasound.The pathological diagnosis was clear in both cases.Both patients underwent breast-conserving surgery and sentinel lymph node biopsy.The two cases received or planned to receive radiotherapy as well as endocrine therapy(tamoxifen).CONCLUSION Breast DCIS arising within a fibroadenoma is rare,but patients treated with radiotherapy and endocrine therapy can have good prognosis.

A rare diagnosis:testicular dysgenesis with carcinoma in situ detected in a patient with ultrasonic microlithiasis

A rare case is presented where a dysgenetic testis with microinvasive carcinoma in situ （CIS, also known as intratubular germ cell neoplasm of unclassified type [IGCNU] and testicular intraepithelial neoplasia [TIN]） with microinvasion to rete testis and the interstitial tissue was found in a 32-year-old man presenting with mild scrotal pain and ultrasonic testicular microlithiasis. Knowledge of the association of ultrasound and CIS is important to diagnose patients at the stage prior to development of an overt germ cell tumor. The patient had three of four disorders considered symptoms of the testicular dysgenesis syndrome （TDS）： a dysgenetic left testicle with CIS, a mild left-sided cryptorchidism （high positioned scrotal hypotrophic testis） and a slightly reduced semen quality. Therefore, it should be kept in mind that a patient with one TDS symptom may harbour the other, even CIS or testicular cancer. Accordingly, patients with one TDS symptom ought to be examined for the presence of the others, and if more that one is present, extra concern is warranted.

DUCTAL CARCINOMA IN SITU OF THE BREAST

Objective: To investigate the clinical characteristics, treatment and prognosis of ductal carcinomain situ (DCIS) of the breast. Methods: Clinicopathological and follow-up data were collected in 52 patients with DCIS. Results: The clinic data showed that 50 patients had signs of breast lumps or/and nipple discharges, 2 patients presented abnormal mammography; 2 patients had lymph node involved; and 14 patients were accompanied with intraductal papillomatosis. All patients were received surgical therapy. The follow-up data showed 1 patient locally recurred after lumpectomy, and was underwent mastectomy again, then cured. There were no patients died of DCIS. Conclusion: Mastectomy should be a standard surgical mode, and the prognosis of DCIS was favorable, but mammography for screening of asymptomatic women should be strengthened to find DCIS.

Histological Grading in Ductal Carcinoma in Situ of the Breast

Objective: To study the significance of histological grading as a prognostic factor in ductal carcinoma in situ of the breast. Methods: According to the Van Nuy’s classification, 32 cases of ductal carcinoma in situ (DCIS) of the breast were divided into three groups. Results: Low grade (well differentiated, low grade DCIS) 12 patients (37.5%); Intermediate grade, 9 patients (28.1%); High grade (poorly differentiated DCIS) 11 patients (34.4%). Among the high grade DCIS, the histologic subtypes were comedo (9 patients), micropapillary (1 patient) and solid (1 patient). The positive expression of c-erbB-2, p53 and MIB-1 in high grade DCIS was higher than that in intermediate and low grade DCIS. The difference between high grade and low grade DCIS was significant (p<0.05). The expression of ER in high grade DCIS was lower than that in intermediate and low grade DCIS. Conclusions: Histological grading of breast ductal carcinoma in situ may be a good prognostic factor.

Comparison of the underestimation rate in cases with ductal carcinoma in situ at ultrasound-guided core biopsy: 14-gauge automated core-needle biopsy vs 11-gauge vacuum-assisted biopsy

Objective： The objective of this study was to compare the underestimation rate of invasive carcinoma cases with ductal carcinoma in situ （DCIS） at percutaneous ultrasound-guided core biopsies of breast lesions between 14-gauge automated core needle biopsy （ACNB） and 11-gauge vacuum-assisted biopsy （VAB）, and analyze the diagnostic advantages and insufficiencies in DCIS between this two methods, and to determine the relationship between the lesion type （masses or microcalcifications on radiological findings ） and DCIS underestimation rate. Methods： We collected 152 breast lesions which were diagnosed as DCIS by retrospectively reviewing data about ultrasound-guided biopsies of breast lesions （from February 2003 to July 2010）. There were 98 lesions in 95 patients by 14-gauge ACNB, and 54 lesions in 52 patients by 11-gauge VAB （The system used in this study called Mammatome, MMT）. The clinical and radiological findings were reviewed; meanwhile all the selected patients had histological results of the biopsies and follow-up surgeries which also achieved the reliable pathological results to compare with the biopsy results. The differences between two correlated histological results defined as underestimation, and the histological DCIS underestimation rates were compared between the two groups. According to the radiological characteristics, each group was classified into two subgroups （masses or micrecalcifications group）, and the differences between subgroups were also analyzed. Results： The DCIS underestimation rate was 45.9% （45/98） for 14-gauge ACNB and 16.6% （9/54） for MMT. According to the lesion type on ultrasonography, DCIS underestimation was 31.0% （26/84） in masses （43.1% using ACNB and 12.1% using MMT; P = 0.003） and 42.6% （29/68） in microcalcifications （48.9% using ACNB and 23,8% using MMT; P = 0,036）, Conclusion： The underestimation rate of invasive carcinoma in cases with DCIS at ultrasound-guided core biopsies is significantly higher for ACNB than for MMT. Furthermore, this difference does not alter among the two lesion types presented on ultrasonography. So ultrasound-guided VAB （MMT system） could be an effective and useful method for the diagnosis of DCIS lesions no matter what the lesion type is.

Expression of E2F-1, Rb and ER in Peripheral Papil-loma and Ductal Carcinoma in Situ of the Breast and its Significance

OBJECTIVE To investigate the correlation of E2F-1, Rb and ER expression with peripheral papilloma （Peri-PM） and ductal carcinoma in situ of the breast （DCIS）, and further explore some molecular mechanisms of the canceratin of Peri-PM.METHODS Imunohistochemistry was used to examine the expression of E2F-1, Rb and ER in 60 Peri-PM, 60 Peri-PM with atypical ductal hyperplasia （Peri-PM with ADH） and 60 DCIS. Normal breast tissues were selected as a control group.RESULTS Based on immunohistochemical staining, the positive rate of E2F-1 expression in Peri-PM, Peri-PM with ADH and DCIS was 21.7%, 46.7% and 78.3% respectively. The positive rate of Rb expression was 83.3 %, 53.9% and 21.7% and the ER expression was 86.7%,61.7% and 55.0%. Significant differences were found among the 3 groups （Peri-PM, Peri-PM with ADH and DCIS） （P〈0.05）. Significant differences existed between any 2 groups （P〈0.05） except for the rate of ER positive expression comparing Peri-PM with ADH verus DCIS （P〉0.05）. The expression of E2F-1 was nega- tively correlated with ER and Rb, and at the same time the expression of ER was positively correlated with Rb. Following the degree of breast epithelial hyperplasia involved and its development into carcinoma, the positive rate of E2F-1 expression displayed an elevating tendency, but that of Rb and ER expression showed a tendency to decline.CONCLUSION The interaction of the 3 indexes studied may play an important role in the conversion of precancerous lesions to early in situ breast carcinoma, and the evaluation of these indexes might provide a valuable basis for screening high-risk cases of Peri-PM.

The Impact of Ethnicity on the Incidence, Tumor Characteristics and Treatment of Ductal Carcinoma in Situ—An 11-Year Clinical Experience at a High Volume Teaching Hospital

Introduction: Screening mammography has led to a marked increase in detection of in situ breast tumors in the United States. The University of Southern California/Van Nuys Prognostic Index (USC/VNPI) predicts the recurrence rates of ductal carcinoma in situ (DCIS);however variations in tumor characteristics, USC/VNPI scores, receptor and human epithelial growth factor receptor (HER)-2/neu status across different ethnicities/races have not been well studied. This study aimed to evaluate the racial trends in incidence, patient demographics, tumor characteristics and treatment variations for patients with DCIS at a high volume teaching hospital. Methods: 395 women underwent surgical intervention for DCIS between 2000 and 2011. Their race/ethnicity was divided into five mutually exclusive categories and demographic and clinicopathological data was collected. Multivariate analysis was performed to evaluate variations in patient and tumor factors with respect to age, size and surgical management among different ethnicities and races. Results: 82.1% of Caucasian women underwent simple mastectomy with sentinel lymph node biopsy (SLNB) while lumpectomy with SLNB was highest in Hispanics (40%, p = 0.005). Overall, there was no significant difference in the incidence of receptor or HER-2/neu positivity, multicentricity, necrosis or grade of DCIS in the various racial groups, but there was a significant racial difference in the USC/VNPI scores (p < 0.001). Conclusion: On a community level, screening detected DCIS accounted for the vast majority of DCIS diagnosed, which reflected national trends. Although no racial variation in DCIS with respect to patient or tumor characteristics was observed, a racial difference in USC/VNPI score was identified among the Hispanic population. Additional studies are required to validate the significance of these findings.

Clinicopathological characteristics,treatments,and prognosis of breast ductal carcinoma in situ with microinvasion:A narrative review

Background:Ductal carcinoma in situ with microinvasion(DCIS-MI)is defined as ductal carcinoma in situ(DCIS)with a microscopic invasive focus≤1 mm in the longest diameter.The current literature is controversial concerning the clinical prognostic features and management of DCIS-MI.This narrative review described recently reported literature regarding the characteristics,treatment,and prognosis of it.Methods:Searching PubMed for relevant articles covering the period of 1982 to 2021 using the following terms by MeSH and free-word:breast cancer,microinvasion,DCIS,DCIS-MI,and invasive ductal carcinoma(IDC).Results:DCIS-MI tends to express more aggressive pathological features such as necrosis,HER2+,ER-or PR-,and high nuclear grade.The overall prognosis of DCIS-MI is typically good,however,some indicators such as young age,HR-,HER2+and multimicroinvasive lesions,were associated with worse prognoses.And there are also conflicting results on the differences between the prognoses of DCIS-MI and DCIS or T1a-IDC.Postoperative chemotherapy and anti-HER2 therapy still have uncertain benefits and are more likely to be used to treat high-risk patients who are HR-orHER2+to improve the prognosis.Conclusion:DCIS-MI has more aggressive pathological features,which may suggest its biological behavior is worse than that of DCIS and similar to early IDC.Although the overall prognosis of DCIS-MI is good,when making decisions about adjuvant therapy clinicians need to give priority to the hormone receptor status,HER2 expression and axillary lymph node status of patients,because these may affect the prognosis and treatment response.

High-grade pancreatic intraepithelial neoplasia diagnosed based on changes in magnetic resonance cholangiopancreatography findings:A case report

BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.

Prognostic signifi cance of transcription factors FOXA1 and GATA-3 in ductal carcinoma in situ in terms of recurrence and estrogen receptor status

Aim:The aim was to analyze the expression of novel biological transcription markers,forkhead-box A1(FOXA1),GATA binding protein 3(GATA-3),and established markers such as Ki-67(MIB-1)and human epidermal growth factor receptor 2(HER2)in estrogen receptor(ER(+))and ER(-)ductal carcinoma in situ(DCIS)patients with/without recurrence.Methods:Two hundred and ninety-one cases of DCIS were retrieved from our pathology database,with complete data available for 219 cases.The follow-up period is from 1988 to 2009.Recurrence is defined in terms of DCIS or invasive carcinoma(IC).No recurrence was seen in 88%(196/219)of cases;12%(26/219)had a recurrence(IC:13,DCIS:13).We are reporting the results of biological marker expression in terms of recurrence and ER status.Results:Our study demonstrates strong expression of GATA-3 in the ER(+)DCIS in recurrence and nonrecurrence groups similar to previously described in IC.A reduced expression of GATA-3 was observed in ER(-)recurrence and nonrecurrence groups.A strong HER2 protein expression,as well as high proliferation index,was seen in recurrence group(DCIS and IC).FOXA1 expression is reduced across the groups though not statistically signifi cant.Conclusion:This is the first study to analyze novel transcription markers FOXA1 and GATA-3 in DCIS.Further work needs to be done on a larger cohort of DCIS cases with recurrence to better understand,which variables are best able to predict recurrence and guide therapy decision strategies.Maintenance of FOXA1 and GATA-3 expression in ER(-)DCIS may offer new promising targets for therapy in future.

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.

LASER SCANNING CYTOMETRIC DNA ANALYSES AND EXPRE- SSION OF P53 PROTEIN,KI67 AND BCL-X IN EARLY AND ADVANCED CARCINOMAS OF THE VOCAL CORD

Objective To study DNA ploidy and genetic changes in the different stages of neoplastic growth in the vocal cord, as well as their biological behavior, for further recognition of the lesions of carcinoma in situ and early carcinoma. Methods 18 tumor lesions of the vocal cord were DNA analyzed by laser scanning cytometry and followed up, and 62 lesions were immunohistochemically investigated for p53, Ki67 and Bcl-X, and with main observation on carcinomas in situ (CISs) and early microinvasive carcinomas (EMICs) which were compared with invasive carcinomas and polyps. Results DNA analysis showed that almost all the CISs and EMICs were diploidy, while 90% invasive carcinomas were aneuploidy. Follow-up data displayed that no one died of the tumor in CIS and EMIC, as well as in the patients with diploidy tumor, and all the patients died of the tumors were with anueploidy tumor. Immunohistochemically, 86% of CIS and EMIC and 91% of invasive carcinoma expressed p53 protein, and the positivities for Ki67 in them were respectively 29% and 27%, which were very significantly different from those of polyps of the vocal cord(P<0.001). In contrast, expression of Bcl-X were decreasing from benign to malignant lesions, and it was lowest in the invasive carcinomas, significantly different from that of polyp(P=0.002). Conclusion The present study showed that there were differences of DNA ploidy and genetic expressions among benign lesions, CISs and EMICs, and invasive carcinomas of the vocal cord, indicating that they might be different in biological entities. CIS of the vocal cord could be considered as a borderline lesion, and is better to receive conservative treatment. Moreover, p53 protein determination combined with Ki67 would be helpful in diagnosis of the carcinomas of the vocal cord.

Clinicopathological significance of chemotactic factor IL-8, MCP-1 and MIP-1α expressions in gallbladder carcinoma

Objective：Gal bladder carcinoma was one of the malignant tumors in the digestive system, characterized by high recurrence and invasion. Recent research indicates that chemotactic factors such as IL-8, MCP-1 and MIP-1αhave played an important role in such aspects as formulation, growth, shifting of the tumor. The aim of this study was to investigate expressions of IL-8, MCP-1 and MIP-1αin gal bladder adenocarcinoma tissues. Methods：Gal bladder adenocarcinoma and noncancerous tissues were routinely formalin-fixed and paraf in-embedded, and in situ hybridization assay for IL-8, MCP-1 and MIP-1αmRNA. Results：（1） The positive rates or the scorings of IL-8, MCP-1 and MIP-1αmRNA were significantly higher in human gal bladder adenocarcinoma than those in human chronic cholecystitis （P〈0.01）. The positive rates or the scorings of three factors were lower in wel-dif erentiatiated gal bladder adenocarcinoma than in poorly-dif erenfiatted ones, whereas there was only one significant dif erence between MCP-1 mRNA （P〈0.05）. The closely positive correlation were found among IL-8, MCP-1 and MIP-1αmRNA. （2） Both the positive rates of IL-8 mRNA and MCP-1 mRNA as wel as their scorings were tightly related to their invasion of the common bile duct and the occurrence of lymph node transfer, moreover, the positive rates of MIP-1αmRNA and its scorings were tightly related to its invasion of liver. （3） Close positive correlation exists not only in IL-8 mRNA and MCP-1 mRNA （r=0.528）, but also in MIP-1αmRNA and IL-8 mRNA （r=0.422）, so does in MCP-1 mRNA and MIP-1αmRNA （r=0.638）. Conclusion：The positive rates or the scorings of IL-8, MCP-1 and MIP-1αmRNA are significantly higher in human gal bladder adenocarcinoma than those in human chronic cholecystitis, and the closely positive correlation are found among them, which suggests that IL-8, MCP-1 and MIP-1αregulate and influence the development and transformation of the gal bladder adencarcinoma together.

Endoscopic features predictive of gastric cancer in superficial lesions with biopsy-proven high grade intraepithelial neoplasia

AIM:To investigate the macroscopic and clinicopathologic features of gastric cancer in patients with biopsy-suggested high grade intraepithelial neoplasia. METHODS:Patients with biopsy-confirmed gastric high grade intraepithelial neoplasia were reviewed from January 2001 to March 2008.Pathologic sections were re-evaluated by two senior pathologists. Patients with an en-bloc resection of the lesion within two months after the diagnosis of high grade intraepithelial neoplasia were enrolled in the study. Clinical manifestations,endoscopic features,biopsy and surgical pathology of all patients were collected and analyzed.The data acquired were subjected to univariate and multivariate analysis. RESULTS:Seventy-two superficial gastric lesions with a pathologic diagnosis of high grade intraepithelial neoplasia based on biopsy specimens were enrolled. True high grade intraepithelial neoplasia was finally proved in 16 lesions and gastric cancer in the rest 56 lesions,most of which(96.4%)were differentiated carcinomas.The result of univariate analysis indicatedthat the size and the presence of marked ulcer plaque or scar in a superficial lesion were independently associated with gastric cancer(P<0.05),when high grade intraepithelial neoplasia was diagnosed by biopsy pathology.The results of multivariate analysis revealed the size greater than 1.5 cm[odds ratio(OR)18.400,P<0.001]and the presence of 5-odd mm ulcer plaque or scar(OR 10.000,P=0.044)were associated with gastric cancer.Accordingly,the sensitivity,specificity and negative predictive value of multivariate analysis for predicting"true high grade intraepithelial neoplasia" was 87.5%,89.3%and 96.2%,respectively. CONCLUSION:Macroscopic findings are of value in differentiation between high grade intraepithelial neoplasia and superficial gastric cancer.This may simplify patient work-up and save costs for patients and healthcare system.

Testicular biopsy： clinical practice and interpretation

Testicular biopsy was considered the cornerstone of male infertility diagnosis for many years in men with unexplained infertility and azoospermia. Recent guidelines for male infertility have limited the indications for a diagnostic testicular biopsy to the confirmation of obstructive azoospermia in men with normal size testes and normal reproductive hormones. Nowadays, testicular biopsies are mainly performed for sperm harvesting in men with non-obstructive azoospermia, to be used for intracytoplasmic sperm injection. Testicular biopsy is also performed in men with risk factors for testicular malignancy. In a subgroup of infertile men, there is an increased risk for carcinoma in situ of the testis, especially in men with a history of cryptorchidism and testicular malignancy and in men with testicular atrophy. Ultrasonographic abnormalities, such as testicular microlithiasis, inhomogeneous parenchyma and lesions of the testes, further increase the risk of carcinoma in situ （CIS） in these men. For an accurate histological classification, proper tissue handling, fixation, preparation of the specimen and evaluation are needed. A standardized approach to testicular biopsy is recommended. In addition, approaches to the detection of CIS of the testis testicular immunohistochemistry are mandatory. In this mini-review, we describe the current indications for testicular biopsies in the diagnosis and management of male infertility.

Roles of micro RNA-140 in stem cell-associated early stage breast cancer

An increasing body of evidence supports a stepwise model for progression of breast cancer from ductal carcinoma in situ(DCIS) to invasive ductal carcinoma(IDC). Due to the high level of DCIS heterogeneity, we cannot currently predict which patients are at highest risk for disease recurrence or progression. The mechanisms of progression are still largely unknown, however cancer stem cell populations in DCIS lesions may serve as malignant precursor cells intimately involved in progression. While genetic and epigenetic alterations found in DCIS are often shared by IDC, m RNA and mi RNA expression profiles are significantly altered. Therapeutic targeting of cancer stem cell pathways and differentially expressed mi RNA could have significant clinical benefit. As tumor grade increases, mi RNA-140 is progressively downregulated. mi R-140 plays an important tumor suppressive role in the Wnt, SOX2 and SOX9 stem cell regulator pathways. Downregulation of mi R-140 removes inhibition of these pathways, leading to higher cancer stem cell populations and breast cancer progression. mi R-140 downregulation is mediated through both an estrogen response element in the mi R-140 promoter region and differential methylation of Cp G islands. These mechanisms are novel targets for epigenetic therapy to activate tumor suppressor signaling via mi R-140. Additionally, we briefly explored the emerging role of exosomes in mediating intercellular mi R-140 signaling. The purpose of this review is to examine the cancer stem cell signaling pathways involved in breast cancer progression, and the role of dysregulation of mi R-140 in regulating DCIS to IDC transition.