CDX-2 immunostaining in primary and secondary ovarian carcinomas.
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ABSTRACT:
SUBMITTER: Tornillo L
PROVIDER: S-EPMC1770317 | biostudies-other | 2004 Jun
REPOSITORIES: biostudies-other
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Project description:The distinction between primary and secondary ovarian tumors may be challenging for pathologists. We performed transcriptomic analysis in order to discriminate between primary ovarian tumors and ovarian metastases after primary breast cancer. We performed genomic analysis on tumor paired samples (breast/ovary) in order to know if genomic profiles could help for the discrimination of primary ovarian tumors and ovarian metastases after primary breast cancer.
2010-04-14 | GSE20565 | GEO
Project description:Although ovarian carcinomas with mutated BRCA1 or BRCA2 are sensitive to platinum compounds, such carcinomas eventually develop platinum resistance. Previously, we showed that acquired resistance to cisplatin in BRCA2-mutated tumors can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. Here, we show that secondary mutations of BRCA1 also occur in BRCA1-mutated ovarian cancer with platinum resistance. We evaluated nine recurrent BRCA1-mutated ovarian cancers previously treated with platinum compounds, including five with acquired platinum resistance, one with primary platinum resistance, and three with platinum sensitivity. Four of the six recurrent platinum-resistant tumors had developed secondary genetic changes in BRCA1 that restored the reading frame of the BRCA1 protein, whereas none of the three platinum-sensitive recurrent tumors developed BRCA1 sequence alterations. We immunohistochemically confirmed restored expression of BRCA1 protein in two cases with secondary mutations. Intriguingly, the case with primary platinum resistance showed back mutation of BRCA1 in the primary tumor and showed another secondary mutation in the recurrent tumor. Our results suggest that secondary mutations in BRCA1 can mediate resistance to platinum in BRCA1-mutated ovarian tumors.
| S-EPMC2674369 | biostudies-literature
Project description:PurposeSecondary somatic BRCA1/2 mutations may restore BRCA1/2 protein in hereditary ovarian carcinomas. In cell lines, BRCA2 restoration mediates resistance to platinum chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors. We assessed primary and recurrent BRCA1/2-mutated ovarian carcinomas to define the frequency of secondary mutations and correlate these changes with clinical outcomes.MethodsNeoplastic cells were isolated with laser capture microdissection, and DNA was sequenced at the site of the known germline BRCA1/2 mutation. When secondary mutations were found that restored wild-type sequence, haplotyping was performed using single nucleotide polymorphisms in tumor and paired lymphocyte DNA to rule out retention of the wild-type allele.ResultsThere were 64 primary and 46 recurrent ovarian carcinomas assessed. Thirteen (28.3%) of 46 (95% CI, 17.3% to 42.6%) recurrent carcinomas had a secondary mutation compared with two (3.1%) of 64 (95% CI, 1.0% to 10.7%) primary carcinomas (P = .0003, Fisher's exact test). Twelve (46.2%) of 26 (95% CI, 28.7% to 64.7%) platinum-resistant recurrences had secondary mutations restoring BRCA1/2, compared with one (5.3%) of 19 (95% CI, 1.2% to 24.8%) platinum-sensitive recurrences (P = .003, Fisher's exact test). Six (66.7%) of nine (95% CI, 34.8% to 87.8%) women with prior breast carcinoma had a recurrent carcinoma with a secondary mutation, compared with six (17.1%) of 35 (95% CI, 8.2% to 32.8%) with no history of breast carcinoma (P = .007, Fisher's exact test).ConclusionSecondary somatic mutations that restore BRCA1/2 in carcinomas from women with germline BRCA1/2 mutations predict resistance to platinum chemotherapy and may also predict resistance to PARP inhibitors. These mutations were detectable only in ovarian carcinomas of women whom have had previous chemotherapy, either for ovarian or breast carcinoma.
| S-EPMC3157963 | biostudies-literature
Project description:BACKGROUND: The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumors after a previous history of breast cancer. METHODS: Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected. The genomic profiles of paired tumors were analyzed using the Affymetrix GeneChip Mapping 50 K Xba Array or Genome-Wide Human SNP Array 6.0 (for one pair), and the data were normalized with ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) algorithm or Partek Genomic Suite, respectively. The transcriptome of paired samples was analyzed using Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays, and the data were normalized with gc-Robust Multi-array Average (gcRMA) algorithm. A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors. RESULTS: In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer. In all pairs, the result of the transcriptomic analysis was concordant with that of the genomic analysis. CONCLUSIONS: In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available.
| S-EPMC2891634 | biostudies-literature
Project description:While papillomavirus (PVs) are an established cause of human cancer, few reports have supported a relationship between PV and canine squamous cell carcinomas (SCCs). Human oncogenic PVs lead to an increased expression of the p16 tumor suppressor protein, and the latter can be demonstrated immunohistochemically to support a likely causal relationship between tumor and PV infection. In the present study, archive samples of canine SCC from different anatomical locations were tested by polymerase chain reaction for the presence of PV DNA and by p16 immunohistochemistry. The aims were to investigate the relationship between p16 expression and presence of PV DNA, in order to assess the utility of p16 overexpression as a biomarker of PV infection in canine SCC. A total of 52 SCCs were included. Nine cases (17.3%) showed moderate p16 immunoreactivity, with no association with tumor degree of differentiation, histotype or mitotic activity. The canPVf/FAP64 primers amplified Canis familiaris PV-1 DNA from 3 out of 52 tumors (5.8%), one cutaneous, one oral and one tonsillar SCC. There was no association between PV presence and p16 immunostaining. These results do not support a significant role of PVs in the development of canine SCCs. Additionally, PV infection was apparently not the cause of the p16 immunostaining observed in a subset of canine SCCs. A better awareness of p16 level of expression and cellular function in canine cancer may help to define its diagnostic and prognostic role.
| S-EPMC4956233 | biostudies-literature
Project description:Primary mucinous ovarian carcinomas (MOC) are notoriously difficult to distinguish from mucinous carcinomas metastatic to the ovary (mMC). Studies performed on small cohorts reported algorithms based on tumor size and laterality to aid in distinguishing MOC from mMC. We evaluated and improved these by performing a large-scale, nationwide search in the Dutch Pathology Registry. All registered pathology reports fulfilling our search criteria concerning MOC in the Netherlands from 2000 to 2011 were collected. Age, histology, laterality, and size were extracted. An existing database covering the same timeline containing tumors metastatic to the ovary was used, extracting all mMC, age, size, laterality, and primary tumor location. Existing algorithms were applied to our cohort. Subsequently, an algorithm based on tumor histology, laterality, and a nomogram based on age and size was created for differentiating MOC and mMC. We identified 735 MOC and 1018 mMC. Patients with MOC were significantly younger and MOC were significantly larger and more often unilateral than mMC. Signet ring cell carcinomas were rarely primary. Our algorithm used signet ring cell histology, bilaterality, and a nomogram integrating patient age and tumor size to diagnose mMC. Sensitivity and specificity for mMC was 90.1% and 59.0%, respectively. Applying existing algorithms on our cohort yielded a far lower sensitivity. The algorithm described here using tumor histology, laterality, size, and patient age has higher sensitivity but lower specificity compared to earlier algorithms and aids in indicating tumor origin, but for conclusive diagnosis, careful integration of morphology, immunohistochemistry, and clinical and imaging data is recommended.
| S-EPMC6515884 | biostudies-other
Project description:ObjectiveThe associations between adrenal histopathology, lateralization studies, and surgical outcomes in primary aldosteronism remain poorly characterized. We examined the value of immunohistochemical analysis of CYP11B2 for evaluation of adrenalectomy outcomes after anatomical versus functional subtyping.DesignA retrospective multicenter study of 277 patients operated for primary aldosteronism who had an adrenalectomy sample available in the Finnish biobanks from 1 January 2000 to 31 December 2019. Adrenal slides from biobanks were analyzed centrally after CYP11B2 and CYP11B1 staining. Clinical data were obtained from patient registries. Histopathological diagnosis and cure after surgery were assessed as outcome measures.ResultsRe-evaluation with CYP11B2 staining changed the histopathological diagnosis in 91 patients (33%). The presence of a CYP11B2-positive adenoma and the use of functional subtyping independently predicted clinical cure of primary aldosteronism. CYP11B2-positive <7 mm nodules were more frequent in patients without clinical cure, whereas CYP11B2-positive micronodules were common in all patients and had no impact on adrenalectomy outcomes. Small CYP11B2-positive nodules and micronodules were equally prevalent regardless of the subtyping method applied. Clinical cure rates were lower and CYP11B2-negative adenomas more common after adrenalectomy based on anatomical imaging than functional studies.ConclusionsIncorporating CYP11B2 staining in histopathological diagnosis enhances the prediction of surgical outcomes in primary aldosteronism. A finding of CYP11B2-positive adenoma is indicative of cure of primary aldosteronism, whereas smaller CYP11B2-positive nodules associate with poorer results at postoperative evaluation. Functional subtyping methods decrease the operations of CYP11B2-negative adenomas and are superior to anatomical imaging in identifying unilateral primary aldosteronism.
| S-EPMC10831582 | biostudies-literature
Project description:BackgroundAccording to WHO, succinate dehydrogenase (SDH)-deficient renal cell carcinoma is characterized by negative immunostaining for SDHB, which remains positive in non-tumor tissue despite germline mutations in the SDHB gene. We now report a patient with a SDHB mutation, c.166_170del (p.Pro56Tyrfs*5) who developed renal cell carcinomas with characteristic morphological features of SDH-deficient renal cell carcinoma but had positive SDHB immunostaining.Case presentationWithin a 6-year period, the patient developed two different renal cell carcinomas, which had characteristic morphological features of SDH-deficient renal cell carcinoma (uniform cells characteristically displaying eosinophilic granular material intermixed with fewer cells exhibiting clear intracytoplasmic inclusions and bland centered nuclei) but displayed immunohistochemistry for SDHB with a cytoplasmic granular positivity (mitochondrial pattern) in tumor cells. For the second case, this was initially interpreted as positive by IHC, but on review some subtle differences were identified.ConclusionsSDHB immunostaining may be positive in renal cell carcinoma associated to germline SDHB deficiency which have other typical morphological features. Immunohistochemistry interpretation may be complex.
| S-EPMC6521540 | biostudies-literature
Project description:Most patients with epithelial ovarian cancer eventually die due to recurrence. However, little is known about the microRNA (miRNA) expression pattern and its involvement in recurrent ovarian cancer. We analyzed miRNA expression profiles related to the recurrence of advanced ovarian high-grade serous carcinoma (HGSC) using miRNA microarrays. Between May 2006 and December 2012, 37 ovarian HGSC patients underwent secondary cyto-debulking surgery at recurrence. Among them, only 8 pairs of primary and recurrent tumor samples were deemed to be adequate for analysis. The expression profiles of primary ovarian HGSC compared with normal ovarian tissue were significantly consistent with those of recurrent ovarian HGSC compared with normal ovarian tissue (correlation coefficient = 0.81, P = 0.0078). Among 31 miRNAs that increased by more than 4-fold in primary tumors compared with normal ovarian tissue, 27 were also significantly increased in recurrent tumor samples. Likewise, among 35 miRNAs that decreased by more than 4-fold in primary tumors compared with normal ovarian tissue, 34 were also significantly decreased in recurrent tumor samples. We identified 60 miRNAs that were significantly increased in recurrent serous ovarian carcinoma compared with primary tumor tissue, including miR-630, miR-370, and miR-575. Additionally, 52 miRNAs were significantly decreased in recurrent samples, including miR-509-3p, miR-514a-3p, and miR-506-3p. Our results demonstrate that primary and recurrent ovarian HGSC displayed similar miRNA expression patterns. Nevertheless, altered miRNA expression could be implicated in the recurrence of ovarian HGSC, and further study is needed to validate these data in independent cases using a homogeneous methodology.
| S-EPMC5342571 | biostudies-literature
Project description:BACKGROUND: It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory. METHODS: We cytogenetically analyzed 110 new cases of ovarian carcinoma of different histological subtypes using karyotyping of G-banded chromosomes and high-resolution comparative genomic hybridization. We first compared the aberration patterns identified by the two genomic screening techniques using the so-called "classical" pathological classification in which the carcinomas are grouped as tumors of types I and II. We also broke down our findings according to the more "modern" classification which groups the carcinomas in five different categories. RESULTS: The chromosomal breakpoints identified by karyotyping tended to cluster to 19p/q and to 11q, but no unquestionably recurrent rearrangement could be seen. Common imbalances were scored as gains from 1q, 3q, 7q, and 8q and losses from 17p, 19q, and 22q. Gain of material from 8q23 and losses from 19q and 22q have previously been described at high frequencies in bilateral and borderline ovarian carcinomas. The fact that they were present both in "precursor" lesions, i.e., borderline tumors, as well as in tumors of more advanced stages, i.e., carcinomas, highlights the possibility of an adenoma-carcinoma sequence in ovarian carcinogenesis. CONCLUSION: Based on the relatively simple genomic changes we identified in the low-grade serous carcinomas examined (n = 7) and which largely corresponded to the aberration pattern formerly identified in borderline tumors, one can interpret the cytogenetic data as supporting the view that the low-grade carcinomas represent a phenotypically more advanced stage of borderline tumors. Whether transition from low-grade to high-grade carcinoma also occurs, is a question about which the genomic data is still inconclusive.
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