Clear Cell Carcinoma Subtypes Research Articles

Multilocular cystic renal neoplasm of low malignant potential in a patient with chronic pyelonephritis and end-stage renal disease: A rare case report

Multilocular cystic renal neoplasm of low malignant potential (MCNLMP) is a rare subtype of clear cell carcinoma having an excellent prognosis. These tumors exhibit distinct morphology and consist of multiple cysts separated by thin septa lined by clear cells with no expansile growth. These cysts, though rare in a setting of chronic pyelonephritis and end-stage renal disease, are usually diagnosed on radiography using the Bosniak classification. But in certain situations where cysts are not visible radiologically, a final diagnosis is made with the help of histopathology and immuno- histochemistry only. We, hereby, report such a rare incidental case of MCNLMP diagnosed on histopathology in a nephrectomy specimen of an elderly male with chronic pyelonephritis and end-stage renal disease.

Seeing beyond the tumor: computed tomography image-based radiomic analysis helps identify ovarian clear cell carcinoma subtype in epithelial ovarian cancer.

To develop and validate a model that can preoperatively identify the ovarian clear cell carcinoma (OCCC) subtype in epithelial ovarian cancer (EOC) using CT imaging radiomics and clinical data. We retrospectively analyzed data from 282 patients with EOC (training set = 225, testing set = 57) who underwent pre-surgery CT examinations. Patients were categorized into OCCC or other EOC subtypes based on postoperative pathology. Seven clinical characteristics (age, cancer antigen [CA]-125, CA-199, endometriosis, venous thromboembolism, hypercalcemia, stage) were collected. Primary tumors were manually delineated on portal venous-phase images, and 1218 radiomic features were extracted. The F-test-based feature selection method and logistic regression algorithm were used to build the radiomic signature, clinical model, and integrated model. To explore the effects of integrated model-assisted diagnosis, five radiologists independently interpreted images in the testing set and reevaluated cases two weeks later with knowledge of the integrated model's output. The diagnostic performances of the predictive models, radiologists, and radiologists aided by the integrated model were evaluated. The integrated model containing the radiomic signature (constructed by four wavelet radiomic features) and three clinical characteristics (CA-125, endometriosis, and hypercalcinemia), showed better diagnostic performance (AUC = 0.863 [0.762-0.964]) than the clinical model (AUC = 0.792 [0.630-0.953], p = 0.295) and the radiomic signature alone (AUC = 0.781 [0.636-0.926], p = 0.185). The diagnostic sensitivities of the radiologists were significantly improved when using the integrated model (p = 0.023-0.041), while the specificities and accuracies were maintained (p = 0.074-1.000). Our integrated model shows great potential to facilitate the early identification of the OCCC subtype in EOC, which may enhance subtype-specific therapy and clinical management.

Multilocular Cystic Neoplasm of Low Malignant Potential: A Rare and Incidental Finding of Clear Renal Cell Variant

Multilocular cystic renal neoplasm is a rare subtype of clear cell carcinoma with an incidence of 1-2 % of all clear cell carcinomas. Morphologically, it shows numerous cysts surrounded by fibrous capsule and septae containing clear cells. The aim of this case report is that the diagnosis is possible solely by histopathological and immunohistochemical evaluation, which aids in distinguishing it from other cystic clear cell entities, as imaging is inconclusive pre-opeartively. Urologists and radiologists should have an adequate understanding such an entity. Almost all the cases are amenable to partial nephrectomy irrespective of the size and there is no documentation regarding the recurrence and metastasis, which mandates less stringent follow up post – operatively compared to clear cell carcinoma.

HNF1β is a sensitive and specific novel marker for yolk sac tumor: a tissue microarray analysis of 601 testicular germ cell tumors

Hepatocyte Nuclear Factor 1 beta (HNF1β) is a transcription factor which plays an important role during early organogenesis, especially of the pancreato-biliary and urogenital tract. Furthermore, HNF1β is an established marker in the differential diagnosis of ovarian cancer and shows a distinct nuclear expression in the clear cell carcinoma subtype. Recently, it has been described in yolk sac tumor, which represents a common component in many non-seminomatous germ cell tumors. Due to its broad histologic diversity, the diagnosis may be challenging and additional tools are very helpful in the workup of germ cell tumors. Immunohistochemistry was used to study HNF1β expression in a tissue microarray (TMA) of 601 testicular germ cell tumors including seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, germ cell neoplasia in situ (GCNIS), and normal tissue. The expression pattern was compared to glypican 3 (GPC3) and α-fetoprotein (AFP), two markers currently in use for the detection of yolk sac tumor. HNF1β showed a distinct nuclear staining in comparison to the cytoplasmic pattern of GPC3 and AFP. The sensitivity and specificity of HNF1β were 85.4% and 96.5%, of GPC3 83.3% and 90.7%, of AFP 62.5% and 97.7%. We conclude that HNF1β allows a reliable distinction of yolk sac tumor from other germ cell tumor components. Therefore, we propose HNF1β as a novel and robust marker in the immunohistochemical workup of testicular germ cell tumors.

Recurrent urothelial carcinoma-like FGFR3 genomic alterations in malignant Brenner tumors of the ovary.

Malignant Brenner tumor is a rare primary ovarian carcinoma subtype that may present diagnostic and therapeutic conundrums. Here, we characterize the genomics of 11 malignant Brenner tumors, which represented 0.1% of 14,153 clinically advanced ovarian carcinomas submitted for genomic profiling during the course of clinical care. At the time of molecular profiling, there was no evidence of a primary urothelial carcinoma of the urinary tract in any case. Cases with transitional-like morphologic features in the setting of variant ovarian serous or endometrioid carcinoma morphology were excluded from the final cohort. Malignant Brenner tumors exhibited CDKN2A/2B loss and oncogenic FGFR1/3 genomic alterations in 55% of cases, respectively; including recurrent FGFR3 S249C or FGFR3-TACC3 fusion in 45% of cases. FGFR3-mutated cases had an associated benign or borderline Brenner tumor pre-cursor components, further confirming the diagnosis and the ovarian site of origin. Malignant Brenner tumors were microsatellite stable, had low tumor mutational burden and exhibited no evidence of homologous recombination deficiency. PIK3CA mutations were enriched with FGFR3 alterations, while FGFR3 wild-type cases featured MDM2 amplification or TP53 mutations. The FGFR3 S249C short variant mutation was absent in 14,142 non-Brenner, ovarian carcinomas subtypes. In contrast to malignant Brenner tumors, FGFR1/2/3 alterations were present in ~5% of non-Brenner, ovarian serous, clear cell and endometrioid carcinoma subtypes, most often as FGFR1 amplification in serous carcinoma or FGFR2 short variant alterations in clear cell or endometrioid carcinomas, respectively. Finally, malignant Brenner tumors had overall distinct genomic signatures compared to FGFR-mutated ovarian serous, endometrioid, and clear cell carcinoma subtypes. This study provides insights into the molecular pathogenesis of malignant Brenner tumors, contrasts the extent of FGFR1/2/3 alterations in ovarian serous, clear cell and endometrioid carcinomas and emphasizes the potential value of novel and FDA-approved, anti-FGFR inhibitors, such as erdafitinib and pemigatinib, in refractory, FGFR3-mutated malignant Brenner tumors.

Molecular subtypes of clear cell carcinoma of the endometrium: Opportunities for prognostic and predictive stratification

ObjectiveOur aim was to characterize the pathological, molecular and clinical outcomes of clear cell carcinoma of the endometrium (CCC). MethodsCCC underwent ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification identifying four molecular subtypes: i) ‘POLEmut’ for ECs with pathogenic POLE mutations, ii) ‘MMRd’, if there is loss of mismatch repair proteins by immunohistochemistry (IHC), iii) ‘p53wt’ or iv) ‘p53abn’ based on p53 IHC staining. Clinicopathologic parameters, immune markers (CD3, CD8, CD79a, CD138, PD-1), ER, L1CAM, and outcomes were assessed. Results52 CCCs were classified, including 1 (2%) POLEmut, 5 (10%) MMRd, 28 (54%) p53wt and 18 (35%) p53abn. Women with p53abn and p53wt CCCs were older than women with MMRd and POLEmut subtypes. p53wt CCC were distinct from typical p53wt endometrioid carcinomas; more likely to arise in older, thinner women, with advanced stage disease, LVSI and lymph node involvement, and a higher proportion ER negative, L1CAM overexpressing tumors with markedly worse outcomes. High levels of immune infiltrates (TILhigh) were observed in 75% of the CCC cohort. L1CAM overexpression was highest within p53abn and p53wt subtypes of CCC. ConclusionCCC is a heterogeneous disease encompassing all four molecular subtypes and a wide range of clinical outcomes. Outcomes of patients with POLEmut, MMRd and p53abn CCC are not distinguishable from those of other patients with these respective subtypes of EC; p53wt CCC, however, differ from endometrioid p53wt EC in clinical, pathological, molecular features and outcomes. Thus, p53wt CCC of endometrium appear to be a distinct clinicopathological entity within the larger group of p53wt ECs.

Analysis of gene expression signatures identifies prognostic and functionally distinct ovarian clear cell carcinoma subtypes.

BackgroundOvarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer (EOC) with distinct pathological, biological, and molecular features. OCCCs are more resistant to conventional treatment regimen of EOC and have the worst stage-adjusted prognosis amongst EOC subtypes. As the OCCC incidence rate in Asian populations has significantly increased in recent decades, it is critical to elucidate its molecular features that could lead to OCCC-tailored therapeutic strategies.MethodsGene expression profiles of 222 OCCC were analyzed by hierarchical clustering and statistical analyses.FindingsWe identified two OCCC gene expression subtypes: EpiCC—epithelial-like, which is associated with early-stage disease, with a relatively higher rate of gene mutations in the SWI/SNF complex; and MesCC—mesenchymal-like, associated with late-stage and higher enrichment of immune-related pathway activity. Genetic, copy number and transcriptomic analyses showed that both EpiCC and MesCC carried OCCC-associated aberrations. The EpiCC/MesCC classification was reproducible in validation cohorts and OCCC cell lines. MesCC tumors had a poorer progression-free survival (PFS) than EpiCC tumors (HR: 3·0, p = 0·0006). Functional assays in cell lines showed that the MesCC subtype was more proliferative and more anoikis-resistant than the EpiCC. By applying the EpiCC/MesCC classification to the TCGA renal clear cell carcinoma cohort, our results indicated interoperability of the subtyping scheme, and revealed preferential drug response of MesCC to bevacizumab.InterpretationThe EpiCC/MesCC classification shows promise for prognostic and therapeutic stratification in OCCC patients and warrants further investigation in the context of OCCC gene expression subtype-tailored treatment strategies.

Perfil inmunohistoquímico de los tumores de células renales

ContextKidney cancer is among the 10 most frequent cancers in the world, each year about 270,000 cases are diagnosed and 116,000 people die from the disease. Approximately 90% of all solid kidney neoplasms are renal cell carcinomas. The incidence in Colombia is approximately 500-1000 cases per year. ObjectiveTo characterize through the use of immunohistochemical markers the different renal cell tumours diagnosed in the pathology laboratory of the San José Hospital (HSJ) and the University Infantil Hospital of San José (HUISJ) in Bogotá. Materials And methodsA retrospective review was performed of the Hematoxylin and eosin and immunohistochemistry slides of all renal cell carcinomas diagnosed in women and men over 18 years in the pathology laboratory of the HSJ and the HUISJ from Bogotá from January 2014 to December 2016. The antibodies used were: CAIX (carbonic anhydrase), RCC (renal cell carcinoma marker), vimentin, CD10, CK7, TFE3 (transcription factor binding to IGHM enhancer 3), CD117, CD15, CK20, cadherin and PAX8. Absolute and relative frequencies of the different markers were reported through univariate and bivariate analyses with a chi-square test. ResultsComparing the expression of statistically significant markers, an immunoprofile resulted for clear cell carcinoma (CRCC) versus RCC chromophobe (ChRCC) as follows: CRCC positive markers: CAIX, vimentin, CD15, CD10, cadherin and negative markers: CK7, CD117; ChRCC positive markers: CK7, CD117, CD10, cadherin and CAIX negative markers: vimentin, CD15. The PAX8 marker was positive or negative in both tumors. ConclusionFive markers demonstrated utility and validity to differentiate between histological subtypes of CRCC and ChRCC. We propose the combination of markers (CAIX, CK7, vimentin, CD15 and CD117) for the differential diagnosis between CRCC versus ChRCC.

Changes in ovarian cancer survival during the 20\xa0years before the era of targeted therapy

BackgroundThe survival of patients with ovarian cancer has improved because of surgery and chemotherapy. This study aimed to estimate the changes in survival rates among Korean women with ovarian cancer prior to the introduction of targeted therapy for ovarian cancer.MethodsData were obtained from the Korea Central Cancer Registry regarding patients who were diagnosed with epithelial ovarian cancer between 1995 and 2014. The relative survival rates were calculated for 5-year periods using the Ederer II method. Cox proportional hazard models were created to assess the associations of demographic and clinicopathological factors with ovarian cancer survival.ResultsDuring the study period, 22,880 women were diagnosed with epithelial ovarian cancer. The 5-year relative survival rate improved from 57.2% during 1995–1999 to 63.8% during 2010–2014 (P < 0.001). Survival outcomes improved between 1995 and 1999 and 2010–2014 for the serous and endometrioid carcinoma subtypes (P < 0.001). However, no improvements were observed for the mucinous and clear cell carcinoma subtypes (P = 0.189 and P = 0.293, respectively). Multivariate analysis revealed that younger age, early stage, recent diagnosis, primary surgical treatment, and non-serous histological subtype were favorable prognostic factors.ConclusionSurvival outcomes have improved for serous and endometrioid epithelial ovarian cancer in the last 20 years. However, no improvement was observed for patients with mucinous and clear cell carcinoma subtypes.

An increased risk of epithelial ovarian cancer in Taiwanese women with a new surgico-pathological diagnosis of endometriosis.

BackgroundEpidemiological evidence of relationships between endometriosis and epithelial ovarian cancer (EOC) has been obtained mainly from Western countries. Our goal was to determine the risk of EOC due to endometriosis in Taiwanese women.MethodsA retrospective cohort study was performed by linking to the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 5,945 women with a new surgico-pathological diagnosis of endometriosis from 2000 to 2010 and 23,780 multivariable-matched controls (1:4) were selected. The Cox regression model adjusted for potential confounders was used to assess the risk of EOC due to endometriosis.ResultsThe EOC incidence rate (IR) of the women with and without endometriosis was 11.64 and 2.66 per 10,000 person-years, contributing to a crude hazard ratio (HR) of 4.48 (95% confidence interval [CI] 2.84-7.06), and HR after adjustment for all confounders (adjusted HR) of 5.62 (95% CI 3.46-9.14); the risk was higher in clear-cell carcinoma subtypes (adjusted HR 7.36, 95% CI 1.91-28.33). The EOC IR of women with endometriosis consistently increased with increasing age, ranging from 4.99 (<30 years) to 35.81 (≥50 years) per 10,000 person-years, contributing to a progressively increased risk of EOC (crude HRs ranging from 2.80 to 6.74 and adjusted HRs ranging from 3.34 to 9.63) compared to age-matched women without endometriosis, whose EOC IR also increased with age. The older women (≥50 years) with endometriosis had a risk of EOC that was higher than both the age-matched women without endometriosis (adjusted HR 9.63, 95% CI 3.27-28.37) and the youngest women (<30 years) with endometriosis (adjusted HR 4.97, 95% CI 1.03-24.09).ConclusionsThese significant findings corroborate the previously reported association between endometriosis and increased risk of EOC. Since the risk of EOC in women with a new surgico-pathological diagnosis of endometriosis constantly increased with age and this increased risk of EOC was more significant in women aged ≥50 years, active and intensive surgical intervention should be taken into consideration for older women with endometriosis.

Claudin7 and moesin in endometrial Adenocarcinoma; a retrospective study of 265 patients

BackgroundMetastasis is the main cause of death in cancer and is a multistep process. Moesin (MSN), a member of the ezrin-rdixin-moesin family and Claudin7 (CLDN7), a tight junction protein, both play a role in tumor cell metastasis. Previously, we found an over-expression of MSN and under-expression of CLDN7 at the mRNA level in uterine serous carcinoma in comparison to uterine endometrioid adenocarcinoma. The purpose of this study is to determine the protein expression of MSN and CLDN7 in endometrial cancer (EC) and to evaluate their prognostic value. Two hundred sixty-five patients with EC were retrieved from the archives. MSN and CLDN7 immunostaining were performed on the tissue paraffin sections. The expression of each antibody was reported and then correlated with clinicopathological prognostic factors including age, tumor grade, tumor stage, lympho-vascular involvement, depth of myometrial invasion, overall survival (OS), disease free survival (DFS) and death of disease (DOD).ResultsMSN and CLDN were expressed in 46% and 52% of overall cases. We observed an association between MSN+ staining and tumor grade, and serous and clear cell carcinoma subtypes (p < 0.001 each). There was an association between CLDN7+ staining and low tumor grade and endometrioid adenocarcinoma subtype (p < 0.001 and 0.001 respectively). However, no association between MSN and CLDN7 expression and outcome including OS, DOD, and DFS was found.ConclusionA significant prognostic value of MSN and CLDN7 in predicting disease outcomes in patients with EC was not demonstrated. Nevertheless, the high percentage of EC cases with MSN and CLDN7 immunoexpression, and their association with tumor grade and subtypes, suggests that these proteins might play a role in tumorigenesis of endometrial adenocarcinomas. Future studies are needed to shed light on their mechanistic properties in EC cells.

IASPP and Chemoresistance in Ovarian Cancers: Effects on Paclitaxel-Mediated Mitotic Catastrophe

iASPP is a specific regulator of p53-mediated apoptosis. Herein, we provided the first report on the expression profile of iASPP in ovarian epithelial tumor and its effect on paclitaxel chemosensitivity. Expression and amplification status of iASPP was examined in 203 clinical samples and 17 cell lines using immunohistochemistry, quantitative real-time PCR, and immunoblotting, and correlated with clinicopathologic parameters. Changes in proliferation, mitotic catastrophe, apoptosis, and underlying mechanism in ovarian cancer cells of different p53 status following paclitaxel exposure were also analyzed. The protein and mRNA expression of iASPP was found to be significantly increased in ovarian cancer samples and cell lines. High iASPP expression was significantly associated with clear cell carcinoma subtype (P = 0.003), carboplatin and paclitaxel chemoresistance (P = 0.04), shorter overall (P = 0.003), and disease-free (P = 0.001) survival. Multivariate analysis confirmed iASPP expression as an independent prognostic factor. Increased iASPP mRNA expression was significantly correlated with gene amplification (P = 0.023). iASPP overexpression in ovarian cancer cells conferred resistance to paclitaxel by reducing mitotic catastrophe in a p53-independent manner via activation of separase, whereas knockdown of iASPP enhanced paclitaxel-mediated mitotic catastrophe through inactivating separase. Both securin and cyclin B1/CDK1 complex were involved in regulating separase by iASPP. Conversely, overexpressed iASPP inhibited apoptosis in a p53-dependent mode. Our data show an association of iASPP overexpression with gene amplification in ovarian cancer and suggest a role of iASPP in poor patient outcome and chemoresistance, through blocking mitotic catastrophe. iASPP should be explored further as a potential prognostic marker and target for chemotherapy.

Study of the Molecular Recognition of Aptamers Selected through Ovarian Cancer Cell-SELEX

BackgroundOvarian cancer is the most lethal gynecological malignancy, and the ovarian clear cell carcinoma subtype (OCCA) demonstrates a particularly poor response to standard treatment. Improvements in ovarian cancer outcomes, especially for OCCA, could be expected from a clearer understanding of the molecular pathology that might guide strategies for earlier diagnosis and more effective treatment.Methodology/Principal FindingsCell-SELEX technology was employed to develop new molecular probes for ovarian cancer cell surface markers. A total of thirteen aptamers with Kd's to ovarian cancer cells in the pico- to nanomolar range were obtained. Preliminary investigation of the targets of these aptamers and their binding characteristics was also performed.Conclusions/SignificanceWe have selected a series of aptamers that bind to different types of ovarian cancer, but not cervical cancer. Though binding to other cancer cell lines was observed, these aptamers could lead to identification of biomarkers that are related to cancer.

Surgical intervention in patients with metastatic renal cancer: current status of metastasectomy and cytoreductive nephrectomy

It is estimated that in 2004 there will be 35,700 new cases of, and 12,480 deaths from, kidney cancer in the US. Since 1950 there has been a 126% increase in the incidence of renal cancer and a 36.5% increase in annual associated mortality. In the past two decades, our understanding of tumors arising from the renal cortex has dramatically expanded owing to advances in cytogenetics and histopathological reclassification. It is now known that renal cell carcinoma (RCC) is a family of neoplasms that possess unique molecular and cytogenetic defects, with 90% of metastases emanating from conventional clear cell carcinoma subtype. In addition to advancing our understanding of RCC, improved abdominal imaging technology has caused a migration of tumor stage and alteration of surgical strategies, with tumors commonly being diagnosed at an earlier stage. Despite these advances, the prognosis for patients with metastatic RCC is poor. Studies that examine combinations of surgery and systemic therapy aim to improve survival in this high-risk group.

Alpha(v)beta(6) integrin-A marker for the malignant potential of epithelial ovarian cancer.

The mechanism(s) responsible for the progression of non-metastatic or borderline ovarian cancer to invasive Grade I/III ovarian cancer is still unknown. An epithelium-restricted integrin, alpha(v)beta(6), is present in malignant epithelia but not in normal epithelia. We studied the relative expression and distribution of alpha(v)beta(6) integrin in early and late-stage invasive (Grade I and Grade III) and non-invasive (benign and borderline) ovarian tumors of serous, mucinous, endometrioid, and clear-cell carcinoma subtypes, to assess its potential as a marker for epithelial ovarian cancer progression. Sixty-six specimens, including eight normal, 13 benign, 14 borderline, 13 Grade I, and 18 Grade III tumors were evaluated by immunohistochemistry (IHC) using a monoclonal antibody (MAb) against alpha(v)beta(6) integrin. Normal ovarian surface epithelium was negative for alpha(v)beta(6) integrin expression. All 45 carcinomas studied were positive, and the staining intensity significantly correlated with the grade of the tumor. The Grade III carcinomas of all types showed strong staining intensity. Only mucinous benign tissues were positive, and no reactivity was observed in benign serous neoplasms. On the basis of these observations, we hypothesize that the expression of alpha(v)beta(6) integrin is associated with epithelial ovarian cancer and that a gradual increase in the expression of the molecule may be a correlative index of the progression of this disease.

Clear cell carcinoma of the endometrium. Prognosis and metastatic pattern.

To establish the prognosis, metastatic pattern, sites of treatment failure, and effect of various treatment modalities, a large series of patients with endometrial clear cell carcinomas (ECCC) was analyzed. Between 1970 and 1992, 181 patients with ECCC were treated. All pathologic slides and medical journals were reviewed. Clinical and histopathologic characteristics and type of treatment were analyzed with the univariate log rank test and multivariate Cox analysis. The 5- and 10-year actuarial disease free survival rates were 43% and 39%, respectively. Pathologic stage, clinical stage, age, and myometrial invasion were the only significant prognostic variables in the univariate analysis. In the multivariate analysis, pathologic stage and age were the sole independent prognostic factors. Two-thirds of the patients with relapse relapsed outside the pelvis. The most frequent extrapelvic sites of relapse were the upper abdomen, lungs, and liver. Four of six patients treated with platinum-containing combination chemotherapy showed response, whereas none of the patients treated with single agent alkylating chemotherapy or progestagens responded. Pathologic stage and age were the two most important prognostic factors in clear cell carcinoma of the endometrium. In Stage I disease, depth of myometrial invasion, age, and subtype of clear cell carcinoma were the sole independent prognostic factors. Two-thirds of the patients relapsed outside the pelvis.

Human ovarian cancer xenografts in nude mice: Characterization and analysis of antigen expression

We have characterized 13 different human ovarian cancer xenografts grown subcutaneously in nude mice. The tumor lines represented 5 histological subtypes: serous (4), mucinous (4), clear-cell carcinoma (1), carcinosarcoma (1) and undifferentiated (3). The specific histology and the degree of differentiation resembled those of the original patients' tumors and were maintained upon serial transfer. Volume doubling times of the xenografts ranged from 3.5 to 15 days. The xenografts were also analyzed for their antigen expression using 20 monoclonal antibodies (MAbs) reactive with 15 tumor-associated antigens. Immunohistochemical examination of tissue sections showed a positive reaction pattern with MAbs 115D8, 140C1, 139H2, 175C5, HMFG1 and HMFG2, each recognizing episialin, as well as with MAbs AUA1, 358.4.32 and 199-157 in xenografts of the serous, mucinous and clear-cell carcinoma subtype. MAb OC125 was reactive with xenografts of the serous subtypes. Other antibodies, such as 494 and OV-TL3 infrequently demonstrated positive reactions. Reactivity of all MAbs was low in the carcinosarcoma and undifferentiated tumor lines. With the exception of AUA1, 495 and 126E5, all MAbs revealed a heterogeneous staining pattern. MAbs against episialin and OC125 predominantly stained the apical site of the tumor cells. Strongest reactivity with almost all histological subtypes was observed with MAbs 115D8, 140C1, 139H2 and AUA1. In cases where we were able to compare the patients' tumor tissue with the respective xenografts, retention of antigen expression was demonstrated in each instance. Release of tumor-associated antigens was shown for CA125 in 2 serous-tumor lines, for CA15.3 in 1 serous-tumor line, and for CEA in 3 lines of the mucinous subtype. This panel of human tumor xenografts could be a valuable tool to determine the potential usefulness of MAb-guided therapy in ovarian cancer.