1/12. Papillary serous carcinoma of the peritoneum: analysis of clonality of peritoneal tumors.Papillary serous carcinoma of the peritoneum (PSCP) is a primary neoplasm of peritoneal origin, and is histologically difficult to differentiate from papillary serous carcinoma of the ovary (PSCO). PSCP is frequently accompanied by many peritoneal tumors, and has been managed as a disseminated disease. In previous reports, however, the clonality of the tumors has not been fully discussed. Recently, the significant roles of the p53 and BRCA1 genes in PSCP have been reported. In this study, we investigated immunohistochemical staining for p53 proteins, and investigated p53 gene mutations, using dna sequencing analysis, to clarify the clonality of PSCP tumors. Immunohistochemically, all the tumor samples demonstrated nuclear overexpression of p53 proteins, and the dna sequencing analysis of the p53 gene showed diverse point mutations at codons 167 and 192 in two of four anatomically different tumors. In conclusion, the possibility of polyclonality of PSCP tumors is suggested.- - - - - - - - - - ranking = 1keywords = mutation (Clic here for more details about this article) |
2/12. Primary peritoneal malignant mixed Mullerian tumors. A clinicopathologic, immunohistochemical, and genetic study.BACKGROUND: Primary peritoneal malignant mixed Mullerian tumors (MMMTs) are rarely reported in the literature. methods: The clinical, pathologic, and immunohistochemical features of five cases of MMMT of female peritoneum were analyzed. The tumors were also investigated for expression of hormone receptors, specific BRCA-1 mutations, and clonality. RESULTS: The patients' ages ranged from 33 to 67 years. They presented with abdominal pain or mass. One case of peritoneal MMMT was associated with a synchronous endometrial carcinoma whereas another case was detected 2 years after the diagnosis of a primary adenocarcinoma of the fallopian tube. One patient died 1 month after diagnosis whereas 2 patients died with disease within 1 year. Both carcinomatous and sarcomatous elements are present in all the tumors. Squamous differentiation was noted in two cases. Heterologous elements, including chondroid, rhabodomyoblastic, and osteoid differentiation were detected in all tumors. Immunohistochemical studies confirm the biphasic differentiation with variable demonstration of neural and smooth muscle differentiation. All five MMMTs were negative for estrogen and progestogen receptors although the related endometrial and tubal carcinomas were positive. heteroduplex analysis used to screen for specific BRCA-1 mutations were negative in all five MMMTs. Clonality study of the two MMMTs found in association with endometrial carcinoma and tubal carcinoma was inconclusive. CONCLUSIONS: Our study confirmed that primary peritoneal MMMTs were aggressive tumors with poor prognosis. The presence of synchronous or metachronous genital carcinomas suggests multifocal tumorigenesis from tissue of same embryologic origin. The lack of hormone receptor in these tumors indicates deviation from hormonal control. Specific BRCA-1 mutations found in ovarian carcinoma in Chinese patients could not be detected in our series.- - - - - - - - - - ranking = 1.5keywords = mutation (Clic here for more details about this article) |
3/12. Three primary malignancies related to BRCA mutation successively occurring in a BRCA1 185delAG mutation carrier.The 185delAG and 5382insC mutations in the BRCA1 gene and the 6174delT mutation in the BRCA2 gene (the Ashkenazi mutations) have been found to be significantly more common among jews of eastern European ancestry (1 in 40, 2.5%) in comparison to the general population (1 in 800 to 1 in 300, 0.12-0.33%). Carriers of these mutations, especially the BRCA1 185delAG mutation, have a significantly increased lifetime risk of breast and ovarian carcinoma and other carcinomas as compared to non-carriers. A case of three primary malignancies related to the BRCA1 185delAG mutation successively occurring in a carrier of this mutation, is described. The patient successively developed breast carcinoma, ovarian micropapillary serous carcinoma and peritoneal papillary serous carcinoma. Immunohistochemical staining results have indicated that these tumors are three separate primary malignancies. This case illustrates that ovarian serous borderline tumors (including micropapillary serous carcinoma) and peritoneal papillary serous carcinomas should be considered, like breast and ovarian carcinomas, tumors expressed in BRCA mutation carriers.- - - - - - - - - - ranking = 8keywords = mutation (Clic here for more details about this article) |
4/12. Molecular genetic analysis of appendiceal mucinous adenomas in identical twins, including one with pseudomyxoma peritonei.pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by mucinous ascites and peritoneal lesions composed of histologically bland to low-grade adenomatous mucinous epithelium within pools of extracellular mucin, often with an associated mucinous adenoma of the appendix. There is evidence that the peritoneal lesions in PMP are clonally derived from the associated appendiceal adenoma. Little is known about the molecular genetic alterations or hereditary factors involved in the development of appendiceal mucinous tumors and PMP. We report the only known example of appendiceal mucinous adenomas in identical twin brothers, one of whom developed PMP. We analyzed the status of the K-RAS and APC genes in these tumors using digital polymerase chain reaction and digital single nucleotide polymorphism (SNP) assay. Identical K-RAS mutations were detected in the appendiceal adenoma and peritoneal tumor from the twin with PMP, whereas the adenoma from the other twin harbored a different mutation. Digital SNP analysis demonstrated loss of heterozygosity of APC only in the adenoma from the twin without PMP but not from the appendiceal or peritoneal tumors of the twin with PMP. The adjacent normal tissue in each case retained both APC alleles. The K-RAS mutational analysis supports the view that PMP is clonally derived from the associated appendiceal mucinous adenoma. The lack of loss of heterozygosity of APC in the adenoma and peritoneal tumor from the twin with PMP suggests that loss of heterozygosity of APC is not necessarily involved in the development of all appendiceal adenomas or PMP. The different types of mutations in K-RAS and the different allelic status of the APC locus in the tumors from both twins suggest that mutation in K-RAS and loss of heterozygosity of APC occurs somatically in adenomas and is independent of the identical genetic background of the twins.- - - - - - - - - - ranking = 2.5keywords = mutation (Clic here for more details about this article) |
5/12. neurofibromatosis 2 and malignant mesothelioma.Mutations of the neurofibromatosis 2 (NF2) tumor suppressor gene cause the inherited disorder NF2 and are also common in malignant mesothelioma, which is not a characteristic feature of NF2. The authors report an asbestos-exposed person with NF2 and malignant mesothelioma. Immunohistochemical analysis of the mesothelioma confirmed loss of expression of the NF2 protein, and comparative genomic hybridization revealed losses of chromosomes 14, 15, and 22, and gain of 7. The authors propose that a person with a constitutional mutation of an NF2 allele is more susceptible to mesothelioma.- - - - - - - - - - ranking = 0.5keywords = mutation (Clic here for more details about this article) |
6/12. BRCA1-related malignancies in a family presenting with von Recklinghausen's disease.BACKGROUND: The association between neurofibromatosis and gynecologic malignancies is rarely reported in the literature. Both BRCA1 and NF1 genes are located on the long arm of chromosome 17. CASE: We have observed a pedigree showing several individuals affected by both type 1 neurofibromatosis (NF1) and breast or coelomatic cancers. The number of individuals affected, their degree of relationship, and the early age at onset were suggestive of an hereditary breast/ovarian cancer syndrome. Linkage analysis was performed in order to establish whether markers in the chromosome 17 region containing the BRCA1 and NF1 loci were shared by affected individuals. Screening for BRCA1 mutations was performed by PTT and SSCP. Analysis of chromosome 17 dna markers in the five family members tested show that three individuals affected by both NF1 and carcinomas share a common haplotype including the NF1 and BRCA1 loci on chromosome 17. mutation analysis showed the presence of a nonsense mutation within BRCA1 exon 12 in two individuals, mother and daughter, affected by breast and peritoneal cancer, respectively, as well as in the son, who had rectal cancer at the early age of 27 years. All three subjects also had NF1. CONCLUSION: The concurrence of NF1 and hereditary breast/ovarian cancer in this family is likely due to the presence of two linked mutations at the NF1 and BRCA1 loci.- - - - - - - - - - ranking = 1.5keywords = mutation (Clic here for more details about this article) |
7/12. Case report: malignant peritoneal mesothelioma in two siblings.BACKGROUND: mesothelioma is a rare tumor, linked with occupational asbestos exposure. This association has been used to explain clustering of cases within families. Newer evidence, however, supports a possible genetic predisposition for this tumor. CASE: Our patient's brother was diagnosed with advanced stage malignant peritoneal mesothelioma in August 1995 at age of 42, he underwent tumor-reductive surgery followed by chemotherapy. He underwent a repeat cytoreductive surgery in September 1996 and further chemotherapy. He died of disease in December 1996. Our patient underwent cytoreductive surgery in May 1999 at age of 49 for advanced stage malignant peritoneal mesothelioma with suboptimal debulking. She received multiple chemotherapy regimens, including most recently experimental targeted agents, for slow progressing disease. She is presently alive with clinical disease 6 years from diagnosis. CONCLUSION: This is the first report of two siblings of different gender with malignant peritoneal mesothelioma and only average environmental asbestos exposure. It is highly likely that the family described in this case report has some form of inherited susceptibility to malignancy cancer gene, HLA type, or tumor suppressor gene mutation.- - - - - - - - - - ranking = 0.5keywords = mutation (Clic here for more details about this article) |
8/12. Sigmoid mesenteric tumour as a manifestation of von Recklinghausen's disease.The gastrointestinal tract may be involved in up to 25% of cases of von Recklinghausen's disease. The authors report such a case in which an 18-year-old girl presented with gastrointestinal symptoms secondary to a tumour in the sigmoid mesentery. There was no family history so it was presumed to be a case of spontaneous mutation. The authors discuss the protein manifestations of neurofibromatosis emphasizing the gastrointestinal presentations and the need for careful surgical management.- - - - - - - - - - ranking = 0.5keywords = mutation (Clic here for more details about this article) |
9/12. Ovarian, peritoneal, and endometrial serous carcinoma: clonal origin of multifocal disease.The clonality of disseminated serous carcinoma involving the ovary, peritoneum, and, occasionally, the endometrium is controversial. Histopathologic examination alone cannot unequivocally distinguish between a monoclonal origin and a multicentric origin. Two patients with peritoneal serous carcinoma with minimal ovarian involvement (one with endometrial serous carcinoma), nine patients with stage III bilateral ovarian carcinoma, and one patient with stage III bilateral carcinosarcoma were studied for clonality. One patient with ovarian carcinoma that recurred after chemotherapy was also studied. Previous analyses of single frozen tumor specimens from these patients had identified different p53 gene mutations in each patient. To test the hypothesis that the disseminated cancers had a monoclonal origin, we assayed dna from numerous foci from each patient to determine whether the known p53 mutation was present in each specimen. Identical mutations were detected in the tumor foci from each patient with peritoneal dissemination and minimal ovarian involvement, including one patient with an endometrial serous carcinoma as well. In all the patients with bilateral ovarian cancer, the genetic change in p53 was identical in both ovarian tumors. Genetic progression was observed in two patients, one of whom showed a loss of heterozygosity involving the p53 gene in a recurrent tumor. In the second patient, a p53 mutation not present in either ovarian tumor was detected in a metastatic tumor from the omentum. These results strongly suggest that disseminated serous carcinomas, whether primary in the ovary, endometrium, or peritoneum, are of monoclonal rather than multicentric origin; that bilateral stage III ovarian cancers are typically of monoclonal origin; and that additional genetic events involving p53 might occur during progression of these tumors.- - - - - - - - - - ranking = 2keywords = mutation (Clic here for more details about this article) |
10/12. Double cancer in a 74-year-old woman: a case report with genetic findings.An autopsy case of double cancer is reported. The patient had undergone right hemicolectomy for colon carcinoma in 1982, and the second cancer was detected in the pancreas in April 1989, which was diagnosed as intraductal papillary adenocarcinoma that is known for its favorable prognosis after surgical resection. However, as the patient did not consent to the operation, she died in August 1994, five years after the diagnosis of the second cancer. Histopathological study revealed neither recurrence nor metastasis of colon carcinoma. The pancreatic carcinoma metastasized to the lung, liver, and peritoneum. DNAs were extracted from paraffin-embedded tissue for molecular pathological examinations. Different mutations were found at codon 12 of the K-ras gene by nucleotide sequencing analysis: one in the colon and the other in the pancreas and lung. Over-expression of p53 protein was also detected in the colon by immunostaining. Replication error was not observed in these three tumors suggesting that a factor(s) other than genetic instability was playing a role in the development of double cancer in this patient.- - - - - - - - - - ranking = 0.5keywords = mutation (Clic here for more details about this article) |
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