Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma.

Mouse monoclonal antibodies PAb 240 and PAb 1801 which specifically immunoprecipitate p53 protein, were used to examine 27 fresh ovarian tumours (16 serous adenocarcinomas, six endometrioid carcinomas, one mucinous adenocarcinoma, one mucinous borderline tumour and three benign adenomas). Eleven out of 16 (69%) serous adenocarcinomas and one endometrioid tumour showed positive staining with one or both antibodies and none of the mucinous or benign tumours stained with either antibody. DNA from tumour and peripheral blood leukocytes was used to identify allelic deletions on chromosome 17p in tumours. 11/12 positively staining tumours showed less of heterozygosity (LOH) on 17p at the nearest informative locus to the p53 gene. In this series of ovarian tumours, LOH on 17p correlates closely with the aberrant expression of the p53 protein in a high proportion of advanced stage serous adenocarcinomas. This observation suggests that the p53 tumour suppressor gene is involved in the evolution of epithelial ovarian cancer (EOC) and may have prognostic significance.     

Allele losses on chromosome 17 in human epithelial ovarian carcinoma

16 epithelial ovarian carcinomas (12 serous, 2 mucinous and 2 endometrioid) and 2 benign ovarian adenomas were studied using recombinant DNA technology to compare loci on chromosome 17 in germ-line and tumour DNA. Four polymorphic probes mapping to 17p and one mapping to 17q were used. There was a high frequency of allele loss on 17q/(77%) and a slightly lower frequency on 17p (69%). These findings probably indicate loss of tumour suppressor genes which are of fundamental importance in the genesis or progression of epithelial ovarian carcinomas.     

Chromosomal changes during development and progression of prostate adenocarcinomas

Chromosomal copy number changes were investigated in 16 prostate carcinomas, 12 prostatic intraepithelial neoplasias (PIN; 4 low-grade and 8 high-grade) adjacent to the invasive tumour areas, and 5 regional lymph node metastases. For this purpose, comparative genomic hybridization (CGH) was performed and a copy number karyotype for each histomorphological entity was created. CGH on microdissected cells from non-neoplastic glands was carried out on 3 different cases to demonstrate the reliability of the overall procedure. None of the non-neoplastic tissue samples revealed chromosome copy number changes. In PIN areas, chromosomal imbalances were detected on chromosomes 7, 8q, Xq (gains), and on 4q, 5q, 8p, 13q and 18q (losses). In the primary tumours, recurrent (at least 25% of cases) gains on chromosomes 12q and 15q, and losses on 2q, 4q, 5q, Xq, 13q and 18q became apparent. Losses on 8p and 6q as well as gains on 8q and of chromosome 7 were also detected at lower frequencies than previously reported. The pooled CGH data from the primary carcinomas revealed a novel region of chromosomal loss on 4q which is also frequently affected in other tumour entities like oesophageal adenocarcinomas and is supposed to harbour a new tumour suppressor gene. Gains on chromosome 9q and of chromosome 16 and loss on chromosome 13q were observed as common aberrations in metastases and primary tumours. These CGH results indicate an accumulation of chromosomal imbalances during the PIN-carcinoma-metastasis sequence and an early origin of tumour-specific aberrations in PIN areas.     

Allelotype of human ovarian cancer.

In order to determine which chromosome(s) carries a tumor suppressor gene(s) for human ovarian cancer, we examined loss of heterozygosity in 37 tumors with a set of polymorphic DNA markers which cover each autosomal chromosome arm partially. Frequent losses were observed in chromosomes 4p (42%), 6p (50%), 7p (43%), 8q (31%), 12p (38%), 12q (33%), 16p (33%), 16q (38%), 17p (46%), 17q (39%), and 19p (34%). In addition to these chromosomes, frequent losses of alleles on chromosomes 6q, 13q, and 19q were observed uniquely in serous and serous papillary cystadenocarcinomas; loss of heterozygosity was detected only rarely on these chromosomal arms in nonserous types of tumors. The average (0.12) of fractional allelic loss seen in mucinous cystadenocarcinoma, which usually has a better prognosis than other types, was much lower than that of other tumor phenotypes including serous cystadenocarcinoma (0.31) and clear cell carcinoma (0.20). These results suggested that (a) a large number of tumor suppressor genes might play a role in ovarian cancer, (b) losses of alleles in different chromosomal regions could account for differences in histopathological features and/or prognoses among patients, and (c) this kind of analysis can contribute to an improved understanding of tumor development and/or progression in human ovarian cancer.     

Borderline epithelial tumours of the ovary--a retrospective analysis of 31 cases

Thirty one cases of epithelial borderline tumours of the ovary recorded over a period of six years were reviewed. The incidence of borderline tumours was 6% in relation to ovarian epithelial malignancies, with serous and mucinous types comprising three fourth of the lesions. The serous tumours were bilateral in 39%, revealed surface growth in 17% and had peritoneal implants in 11% of cases. The mucinous tumours were bilateral in 11% and had associated pseudomyxoma peritonei in 22% of cases. Nuclear grade appeared to correlate with extraovarian spread and surface growth in the serous borderline tumours, but not in the mucinous borderline tumours. The endometrioid borderline tumours and mixed epithelial borderline tumours were rare lesions. Twenty one patients (68%) presented in Stage-la. Surface growth correlated with recurrences. The prognosis remained good in serous borderline tumours even in the presence of implants as these were non-invasive. The mean disease free survival was 43.03 months. There was no statistical difference in disease free survival of patients with and without implants.     

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.     

Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K-ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary

To clarify the role of the p53 tumor suppressor gene in the development of human ovarian epithelial tumors and to study the association of p53 alterations with K-ras activation, a series of 70 common epithelial ovarian tumors from Japanese patients was studied. These included 31 serous adenocarcinomas, 12 mucinous adenocarcinomas, 5 mutinous tumors of borderline malignancy, 13 endometrioid adenocarcinomas, and 9 clear cell carcinomas. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 14 of 36 (39%) informative cases by restriction fragment length polymorphism analysis and by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction(PCR)-amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by SSCP analysis of PCR-amplifled fragments. Mutations were found in 22 of 70 (31%) ovarian tumors, including 1 of 5 mucinous tumors of borderline malignancy. Mutations were subsequently characterized by direct sequencing. Single missense base substitutions were detected in 13 ovarian carcinomas and in one case of mucinous tumor of borderline malignancy. Short (1-8 bp) deletions and insertions were found in 8 cases. Mutations in the p53 gene occurred more frequently in serous adenocarcinomas (14/31, 45%) than in all nonserous types of malignant epithelial tumors combined (7/34, 21%;P=0.032). Point mutations in K-ras were identified by dot blot hybridization analysis of PCR-amplified fragments with mutation-specific oligonucleotides and by direct sequencing. The overall frequency of K-ras mutations was 19/70 (27%).K-ras mutations were found in 12 of 17 (71%) mucinous tumors (8/12 mucinous carcinomas [67%] and 4/5 mucinous tumors of borderline malignancy [80%]), and occurred more frequently than in serous carcinomas (4/31, 13%;P=0.00009) or in all nonmucinous types of ovarian epithelial tumors combined (7/53, 13%; p=0.00002). These data suggest that different combinations of oncogenes and/or tumor suppressor genes may be involved in the genesis and development of histologically distinct categories of common epithelial tumors of the human ovary.     

Amplicon profiles in ovarian serous carcinomas

Ovarian serous carcinoma is the most common and lethal type of ovarian cancer and its molecular etiology remains poorly understood. As an ongoing effort to elucidate the pathogenesis of ovarian serous carcinomas, we assessed the DNA copy number changes in 33 high-grade serous carcinomas and 10 low-grade serous tumors by using a genome-wide technique, single nucleotide polymorphism array, performed on affinity-purified tumor cells from fresh surgical specimens. Compared to low-grade tumors, high-grade serous carcinomas showed widespread DNA copy number changes. The most frequent alterations were in loci harboring candidate oncogenes: cyclin E1 (CCNE1), AKT2, Notch3 and PIK3CA as well as in novel loci, including 12p13, 8q24, 12p13 and 12q15. Seven amplicons were selected for dual color fluorescence in situ hybridization analysis in approximately 90 high-grade serous carcinomas and 26 low-grade serous tumors, and a high level of DNA copy number gain (amplification) was found in CCNE1, Notch3, HBXAP/Rsf-1, AKT2, PIK3CA and chr12p13 occurring in 36.1%, 7.8%, 15.7%, 13.6%, 10.8% and 7.3% of high-grade serous carcinomas. In contrast, we did not observe high level of ERBB2 amplification in any of the samples. Low-grade tumors did not show DNA copy number gain in any of the loci, except in 2 (8%) of 24 low-grade tumors showing low copy number gain in the Notch3 locus. Taken together, our results provide the first comprehensive analysis of DNA copy number changes in highly pure ovarian serous carcinoma. These findings may have important biological and clinical implications.     

Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer

Recurrent chromosome 8q gain in ovarian carcinoma is likely to reflect the existence of multiple target loci, as the separate gain of chromosome bands 8q21 and 8q24 has been reported in independent studies. Since tumor protein D52 (TPD52) has been identified as a chromosome 8q21 amplification target in breast and prostate carcinoma, we compared TPD52 expression in normal ovarian epithelium (n = 9), benign serous adenomas (n = 11), serous borderline tumors (n = 6) and invasive carcinomas of the major histologic subtypes (n = 57) using immunohistochemistry. These analyses revealed that all normal ovarian epithelium samples and benign serous tumors were predominantly TPD52-negative, whereas TPD52 was overexpressed in most (44/57; 77%) ovarian carcinomas regardless of histologic subtype. TPD52 subcellular localization was predominantly cytoplasmic, although nuclear localization was also frequently observed in mucinous and clear cell carcinomas. In an independent cohort of stage III serous carcinomas (n = 18), we also directly compared in situ TPD52 expression using immunohistochemistry and TPD52 copy number using interphase FISH analyses. This revealed that TPD52 dosage and TPD52 expression were significantly positively correlated. TPD52 therefore represents a novel molecular marker in ovarian cancer, which is broadly expressed across the different histologic subtypes and whose upregulation frequently reflects increased TPD52 copy number.     

Early loss of heterozygosity on 17q in ovarian cancer. The Abe Ovarian Cancer Genetics Group.

We have studied 146 ovarian tumours (94 carcinomas, 22 tumours of low malignant potential and 30 benign tumours) for evidence of allele loss on chromosome 17p and 17q sufficient to imply the proximity of a tumour-suppressor gene. We have examined two polymorphic loci (YNZ22.2 and BHP53) on 17p13 and one on chromosome 17q (17q23-qter). Loss of heterozygosity (LOH) was detected in 34/63 (54%) informative malignant tumours at YNZ22.2 and 22/47 (47%) at BHP53; on 17q, 45/64 (70%) had LOH. Allele loss was detected in a small number of benign and borderline tumours. There was a statistically significant difference between the patterns of allele loss in serous and endometrioid groups of tumours, and allele loss occurred with significantly greater frequency on 17q than on 17p. Comparison of all malignant tumours presenting with either localized (FIGO stage I/II) or widespread (FIGO stage III/IV) disease showed that, particularly on 17q, allele loss increases in the more advanced stages. The p53 tumour-suppressor gene is implicated in ovarian carcinogenesis, and our findings suggest that an important tumour-suppressor gene may be located in the region 17q23-qter. Loss of function in this gene may be responsible for the frequently observed rapid progression of serous-type adenocarcinomas to an advanced stage.     

Allele loss from large regions of chromosome 17 is common only in certain histological subtypes of ovarian carcinomas.

Using a panel of ten polymorphic markers, we examined the frequency of loss of heterozygosity (LOH) on chromosome 17 in 55 sporadic ovarian tumours. LOH on 17p and 17q was observed to be 50% and 62% respectively. LOH at D17S5 was detected in 24/36 (67%) of malignant cases and in 19/43 (44%) at TP53; the marker D17S855 intragenic to the BRCA1 gene showed allele loss in 50% (20/40) cases. The data presented here suggest that loss of the whole chromosome 17 is a relatively frequent event (30%) in ovarian carcinomas and this observation is especially frequent for serous, transitional cell and anaplastic histological subtypes. Mucinous and endometrioid ovarian tumours showed only short interstitial deletions (4/11, 36%). The overall frequency of the short deletions was relatively low (7/43, 16%) in our panel of carcinomas. Amplification of c-erbB-2/neu oncogene was detected in 32% (11/34) of the carcinomas tested; the gene was amplified only in those histological subtypes in which high incidence of LOH on chromosome 17 was observed, and was associated with advanced stages of the disease. We conclude that different histological types of tumour may have different aetiological mechanisms, and tumour-suppressor genes on chromosome 17 might be associated specifically with serous and transitional cell ovarian carcinomas.     

Comparative genomic hybridization detects many recurrent imbalances in central nervous system primitive neuroectodermal tumours in children

A series of 23 children with primitive neuroectodermal tumours (PNET) were analysed with comparative genomic hybridization (CGH). Multiple chromosomal imbalances have been detected in 20 patients. The most frequently involved chromosome was chromosome 17, with a gain of 17q (11 cases) and loss of 17p (eight cases). Further recurrent copy number changes were detected. Extra copies of chromosome 7 were present in nine patients and gains of 1q were detected in six patients. A moderate genomic amplification was detected in one patient, involving two sites on 3p and the whole 12p. Losses were more frequent, and especially involved the chromosomes 11 (nine cases), 10q (eight cases), 8 (six cases), X (six patients) and 3 (five cases), and part of chromosome 9 (five cases). These recurrent chromosomal changes may highlight locations of novel genes with an important role in the development and/or progression of PNET.     

Alteration of p53 gene in ovarian carcinoma: clinicopathological correlation and prognostic significance.

Inactivation of the tumour-suppressor gene p53 has been demonstrated in a variety of human tumours. We extracted DNA from paraffin-embedded tissues of 67 ovarian carcinoma samples (54 primary tumours, seven metastases and six tumours obtained after chemotherapy), and analysed allelic losses and mutations of the p53 gene using single-strand conformation polymorphism (SSCP) analysis of DNA fragments amplified by a polymerase chain reaction (PCR). Allelic loss was observed in 24 of 32 informative cases. The mutation was detected in 14 of 54 primary ovarian carcinomas: eight serous cystadenocarcinomas (SCA), 42%), five endometrioid adenocarcinomas (EA, 42%) and one mucinous cystadenocarcinoma (14%). The incidence of the alteration was higher in SCA and EA than in other histological types, but the difference was not statistically significant. The incidence of p53 gene abnormalities in ovarian carcinomas tended to be increased in patients with disease advanced (over FIGO stage II). Mutations were found in exons 5 and 7 only and consisted mainly of single nucleotide substitutions [9 or 14 (64%) in exon 7; 4 of 14 (29%) in exon 5]. In 13 of 14 cases, p53 gene mutations occurred concomitantly with losses of the normal allele. The status of the p53 gene in metastases and the tumours obtained after chemotherapy was identical to that in the primary tumours. The presence of p53 gene mutation did not correlate with histological grade, response to primary therapy and survival. These findings suggest that mutational alterations of the p53 gene are involved in the development of a significant proportion of some ovarian carcinomas (SCAs or EAs), especially in advanced stages. However, they may not be a marker predicting the biological behaviour or the outcome of the disease.     

Chromosomal abnormality in hepatocellular carcinoma by comparative genomic hybridisation in Taiwan

The elucidation of the genetic changes of hepatocellular carcinoma (HCC) is very important for understanding the molecular mechanism of liver carcinogenesis. In order to identify the gains or losses in DNA sequence copy number in HCC, we used comparative genomic hybridisation to study 40 cases (44 tumours) of HCC. Tumour DNA and DNA from non-neoplastic liver tissue were labelled with different fluorochromes and then simultaneously hybridised to normal metaphase spread chromosomes. An image acquisition system was used to quantitate signal intensities contributed by tumour and reference DNA along the entire length of each chromosome. Regions of amplification and deletion were demonstrated as quantitative alterations. Losses were prevalent on chromosome regions 16q (43%), 17p (20%), 13q (20%), 4q (15%) and 8p (15%). Gains frequently occurred on 8q (30%), 1q (20%), 6p (20%) and 17q (18%). Hepatitis B virus carriers had a significantly higher frequency of losses on chromosome 16q. Furthermore, the minimal region of losses was narrowed down to 16q11-q22. This study confirms the presence of previously known chromosomal aberrations in HCC and highlights a new significant correlation between losses on chromosome 16q and hepatitis B virus carriers.     

Allelotype analysis of common epithelial ovarian cancers with special reference to comparison between clear cell adenocarcinoma with other histological types.

Determination of the histological type of epithelial ovarian cancer is clinically important to predict patient prognosis. To estimate accurately the chromosomal regions that frequently show loss of heterozygosity (LOH) in each histological type, LOH at 55 loci on 38 chromosomal arms was examined by means of laser capture microdissection and PCR-LOH analysis in 45 epithelial ovarian cancers composed of clear cell adenocarcinoma (CCA), serous adenocarcinoma (SEA), endometrioid adenocarcinoma (EMA) and mucinous adenocarcinoma (MUA). In addition, p53 (exons 5 - 8) gene mutations and the nuclear immunoreactivity of p53 proteins in these tumors were examined by PCR-SSCP and immunohistochemistry. In CCA, LOH was detected primarily on 1p (69%) followed by 19p (45%) and 11q (43%). On the other hand, in SEA, LOH was detected in at least 50% of cases on 1p, 4p, 5q, 6p, 8p, 9q, 12q, 13q, 15q, 16p, 17p, 17q, 18p, 18q, 19p, 20p and Xp. The incidences of LOH on 5q, 12q, 13q and 17p were significantly lower in CCA than in SEA (P = 0.019, 0.031, 0.0035 and 0.012). EMA showed a tendency for frequent LOH on 7p, whereas MUA showed significantly high occurrence of LOH at 17p13.1. The incidences of p53 mutation and p53 nuclear immunoreactivity also differed between CCA and SEA: 0% and 7% in the former and 64% and 45% in the latter (P = 0.0006 and 0.039). These findings clarify that there are differences in LOH distribution patterns among different histological subtypes of epithelial ovarian cancer. In CCA, p53 tumor-suppressor gene (TSG) is not involved in carcinogenesis and tumor-suppressor genes located on 1p are considered to play an important role in tumor development.     

Allelotype Analysis of Common Epithelial Ovarian Cancers with Special Reference to Comparison between Clear Cell Adenocarcinoma with Other Histological Types

Determination of the histological type of epithelial ovarian cancer is clinically important to predict patient prognosis. To estimate accurately the chromosomal regions that frequently show loss of heterozygosity (LOH) in each histological type, LOH at 55 loci on 38 chromosomal arms was examined by means of laser capture microdissection and PCR-LOH analysis in 45 epithelial ovarian cancers composed of clear cell adenocarcinoma (CCA), serous adenocarcinoma (SEA), endometrioid adenocarcinoma (EMA) and mucinous adenocarcinoma (MUA). In addition, p53 (exons 5–8) gene mutations and the nuclear immunoreactivity of p53 proteins in these tumors were examined by PCR-SSCP and immunohistochemistry. In CCA, LOH was detected primarily on 1p (69%) followed by 19p (45%) and 11q (43%). On the other hand, in SEA, LOH was detected in at least 50% of cases on 1p, 4p, 5q, 6p, 8p, 9q, 12q, 13q, 15q, 16p, 17p, 17q, 18p, 18q, 19p, 20p and Xp. The incidences of LOH on 5q, 12q, 13q and 17p were significantly lower in CCA than in SEA ( P =0.019, 0.031, 0.0035 and 0.012). EMA showed a tendency for frequent LOH on 7p, whereas MUA showed significantly high occurrence of LOH at 17p13.1. The incidences of p53 mutation and p53 nuclear immunoreactivity also differed between CCA and SEA: 0% and 7% in the former and 64% and 45% in the latter ( P =0.0006 and 0.039). These findings clarify that there are differences in LOH distribution patterns among different histological subtypes of epithelial ovarian cancer. In CCA, p53 tumor-suppressor gene (TSG) is not involved in carcinogenesis and tumor-suppressor genes located on 1p are considered to play an important role in tumor development.     

Expression of placental alkaline phosphatase in epithelial ovarian tumours

The expression of placental alkaline phosphatase in 116 ovarian epithelial tumours was examined in formalin-fixed tissues used for routine histopathologic examination. In the total material, 51% of the tumours displayed positive immunoreactivity, as described by the monoclonal anti-placental alkaline phosphatase antibody C2, with similar incidence (46-67%) in the four major groups of the adenocarcinomas, i.e., serous, mucinous, endometrioid and mesonephric tumours. By use of a histochemical staining index the mucinous and mesonephric tumours demonstrated a more intense staining (2.1 and 2.6) compared to the serous and endometrioid tumours (0.9 and 1.5). The relevance of the findings is discussed in relation to the use of monoclonal antibody technologies for radioimmunolocalization and radioimmunotherapy.     

Cigarette smoking and the risk of invasive epithelial ovarian cancer in a prospective cohort study

Few cohort studies have examined the association between cigarette smoking and ovarian cancer risk, either overall, or by histological subtype. In relation to the latter, it has been suggested that mucinous ovarian tumours may be aetiologically unrelated to the other types of epithelial tumours and that their respective associations with cigarette smoking may differ. We examined the association between smoking and ovarian cancer risk using data from participants in a randomised controlled trial of screening for breast cancer involving 89,835 women aged 40-59 years at recruitment. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). During an average of 16.5 years of follow-up, we observed 454 incident cases of ovarian cancer (184 serous, 67 endometrioid, 32 mucinous, 171 other or unknown). We found that women who had smoked for several decades had an approximately two-fold increased risk of epithelial ovarian cancer. Relative to never-smokers, women who had smoked for 40 years or more were at the highest risk (RR=2.50, 95% CI=1.37-4.56). The association with non-mucinous tumours was similar to that observed overall. For mucinous tumours, a two-fold increased risk was observed with smoking of shorter duration, although the number of mucinous tumours in our data-set was small. Long-term cigarette smoking may be associated with an increased risk of epithelial ovarian tumours.     

Frequent gene dosage alterations in stromal cells of epithelial ovarian carcinomas

Stromal cells are an active and integral part of epithelial neoplasms. We have previously observed allelic imbalance on chromosome 3p21 in both stromal and epithelial cells of ovarian tumors. This study was designed to explore gene dosage alterations throughout human chromosomes from stromal and epithelial cells of epithelial ovarian carcinomas. Thirteen stromal and 24 epithelial samples, microdissected from epithelial ovarian carcinomas, were analyzed using multiplex ligation-dependent probe amplification technique. Analysis covered 110 cancer related genes. Frequent genetic alterations were detected both in the stroma and epithelium of ovarian carcinomas. The mean number of altered genes per tumor was 10.8 in stroma and 23.6 in epithelium. In the stroma, the mean number of gains was 6.6 and of losses 4.2 and in the epithelium 13.7 and 9.9. The high number of changes associated with advanced tumor stage (p = 0.035) and death due to ovarian cancer (p = 0.032). The most frequent alteration was the deletion of the deleted in colorectal carcinoma (DCC) on chromosome 18q21.3 in 62% of samples. Loss of DCC was related to endometrioid subtype (p = 0.033). Large chromosomal aberrations were detected on the basis of alterations in adjacent genes. Most importantly, 38 genes showed similar genetic alterations (gain-gain or loss-loss) in stromal and epithelial compartments of 11 tumor pairs. Thus, frequent genetic alterations in stromal cells of epithelial ovarian carcinomas resembled those of malignant epithelial cells and may indicate a common precursor cell type. Epithelial-mesenchymal transition may generate transformed cancer cells and modify the tumor microenvironment with distinct properties.