Microsatellite alterations on human chromosome 11 in in situ and invasive breast cancer: A microdissection microsatellite analysis and correlation with p53, ER (estrogen receptor), and PR (progesterone receptor) protein immunoreactivity

Shen, Kuo‐Liang; Yang, Lien‐Shun; Hsieh, Hsi‐Lung; Chen, Cheng‐Jueng; Yu, Jyh‐Cherng; Tsai, Nu‐Man; Harn, Horng‐Jyh

doi:10.1002/1096-9098(200006)74:2<100::aid-jso5>3.0.co;2-o

Cited by 20 publications

(11 citation statements)

References 24 publications

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“…However, the reported rates of MSI in sporadic breast cancer vary greatly (Aldaz et al, 1995;Contegiacomo et al, 1995;Cui et al, 1998;de Marchis et al, 1997;Fujii et al, 1998;Jonsson et al, 1995;Paulson et al, 1996;Rosenberg et al, 1997;Rush et al, 1997;Shaw et al, 1996;Shen et al, 2000;Siah et al, 2000;Toyama et al, 1996a,b;Walsh et al, 1998;Yee et al, 1994;Zenklusen et al, 1994), possibly due to differences in the degree of cancer progression and in the methods and markers used for analysis. Using five markers previously shown to be highly unstable in breast cancer (Paulson et al, 1996;Yee et al, 1994), we observed a relatively high mutation rate for each marker (from 10 to 20%).…”

Section: Discussionsupporting

confidence: 91%

“…In the majority of cases, the cause of this disease is still unknown even though two breast cancer susceptibility genes (BRCA1 and BRCA2), mutated in approximately 5 -10% of all breast cancers, have been identified. Recent studies indicate that a substantial fraction of breast tumors have frequent microsatellite instability (MSI) (Aldaz et al, 1995;Contegiacomo et al, 1995;Cui et al, 1998;de Marchis et al, 1997;Fujii et al, 1998;Jonsson et al, 1995;Paulson et al, 1996;Rosenberg et al, 1997;Rush et al, 1997;Shaw et al, 1996;Shen et al, 2000;Siah et al, 2000;Toyama et al, 1996a,b;Walsh et al, 1998;Yee et al, 1994;Zenklusen et al, 1994), a phenomenon tightly associated with mismatch repair (MMR) deficiency (Parsons et al, 1993;Strand et al, 1993) and initially observed in cells from hereditary non-polyposis colorectal cancers (HNPCC) as well as some sporadic colorectal tumors (Aaltonen et al, 1993;Thibodeau et al, 1993). Defective MMR has also been identified in other types of cancer associated with MSI, including sporadic gastric (Bevilacqua and Simpson, 2000;Fleisher et al, 1999;Leung et al, 1999) and endometrial cancers (Esteller et al, 1998Gurin et al, 1999;Katabuchi et al, 1995;Salvesen et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability

et al. 2002

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Breast cancer is the most common cancer in women, but its pathogenesis is still unclear. Microsatellite instability (MSI) has been identified in breast cancer cells, suggesting an association with mismatch repair defects. To test this hypothesis, we investigated MSI, protein expression of hMSH2 and hMLH1, as well as genetic and epigenetic modifications of these two genes in 32 sporadic breast tumors. MSI was identified in 15 cases. Immunohistochemistry analysis revealed that all MSI cases but one had lower than normal expression of hMSH2 (nine cases), hMLH1 (12 cases), or both (seven cases). In tumors with MSI, both genetic and epigenetic modifications of these mismatch repair genes were also identified. Eight cases harbored mutations or polymorphisms in hMSH2 and hMLH1, and 10 exhibited hypermethylation in the promoter region of hMLH1. These results suggest that both genetic and epigenetic alterations of hMSH2 and especially of hMLH1 contribute to genomic instability and tumorigenesis in sporadic breast cancer.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability

et al. 2002

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“…MSI positive colon cancers have been associated with very low levels of estrogen receptors, 54 while studies in breast carcinoma have yielded controversial results. 55,56 However, to the best of our knowledge, there is no data analyzing the relationship between MSI and estrogen exposure in endometrial carcinoma. In our study, it appears that patients with tamoxifen exposure had a lower prevalence of PTEN mutations (9 vs 40% in the control group) and MSI (8 vs 29% among controls).…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological and molecular analysis of endometrial carcinoma associated with tamoxifen

et al. 2008

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Use of tamoxifen for treatment and prevention of breast cancer is becoming increasingly common. Tamoxifen has been associated with increased risk of endometrial carcinoma, although the exact mechanism of action is unknown. The aim of our study was to seek a possible correlation between endometrial carcinoma, tamoxifen exposure and MSI, PTEN, b-catenin and K-ras abnormalities. A group of 18 patients with endometrial carcinoma following treatment with tamoxifen were selected. A control group included 15 patients with endometrial carcinoma and associated ovarian hyperthecosis and one patient with endometrial carcinoma and adult granulosa cell tumor of the ovary, chosen because both conditions are associated with increased production of estrogen and increased risk of endometrial carcinoma development. The second control group included 27 randomly selected consecutive patients with endometrial carcinoma without identifiable associated conditions. Immunostaining for b-catenin was performed on all cases; DNA was extracted and amplified by PCR with primers for b-catenin, K-ras and PTEN genes. BAT-25 and BAT-26 were analyzed to assess for MSI. There were 16 endometrioid endometrial carcinomas, one mixed carcinoma and one clear cell carcinoma among patients in the tamoxifen group. All patients with ovarian hyperthecosis and adult granulosa cell tumor had endometrioid endometrial carcinoma. In the random control group, there were 26 endometrioid endometrial carcinomas and one carcinosarcoma. Immunohistochemical and mutational analysis for b-catenin showed abnormalities in 4/11 (36%) and 3/10 (30%) informative cases in the tamoxifen group; 7/16 (44%) and 4/15 (27%) informative cases, respectively in the ovarian hyperthecosis group and 1/27 random control cases (4%) (Po0.05). Patients with tamoxifen exposure had more K-ras mutations and fewer PTEN mutations and MSI as opposed to controls, but the results were not statistically significant. In conclusion, there was a direct relationship between tamoxifen exposure and overexpression of b-catenin oncoprotein, which is known to play a major role in the pathogenesis of estrogen-driven, type I endometrial adenocarcinoma. Modern Pathology (2008) 21, 925-936; doi:10.1038/modpathol.2008 published online 23 May 2008 Keywords: endometrial carcinoma; pathogenesis; estrogen; tamoxifen; b-catenin Endometrial carcinoma is the most common malignancy of the female genital tract in the United States. It has been traditionally classified into two categories: type I tumors, estrogen driven and characterized by endometrioid morphology (70-80%) and type II tumors, which are unrelated to estrogen and show serous/clear cell differentiation.

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“…Previous studies have implied that longer alleles of microsatellite polymorphisms may destabilize mRNA and thus decrease gene expression as has been demonstrated for microsatellites in chromosome 11 and p53 and estrogen receptor expression (38). A similar effect has been shown for CTLA-4 +642(AT) n by a study showing an association of longer microsatellite alleles with increased IL-2 expression and T-cell proliferation as well as an increased incidence of myasthenia gravis, suggesting a decreased regulatory effect of CTLA-4 (39,40).…”

Section: Discussionmentioning

confidence: 99%

The Impact of Costimulatory Molecule Gene Polymorphisms on Clinical Outcomes in Liver Transplantation

Marder¹,

Schröppel²,

Lin³

et al. 2003

American Journal of Transplantation

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CTLA-4 and CD28 deliver opposing signals for T-cell proliferation. We examined single nucleotide polymorphisms (SNPs) CTLA-4 -318C/T and CD28 IVS3 +17T/C for associations with acute rejection in liver transplant recipients. These and two other polymorphisms in CTLA-4 [microsatellite polymorphism +642(AT) n and SNP +49 A/G] were also analyzed for influence on graft survival. Two hundred and eleven liver transplant recipient genotypes were determined by direct sequencing or restriction fragment length polymorphism analysis of PCR-amplified genomic DNA. Mean graft survival for patients with the GG genotype of CTLA-4 +49 A/G was 58.5 -6.0 months compared with 70.3 -4.0 months and 73.8 -2.8 months 2.8 months for the AA and AG genotypes, respectively (p = 0.0055). This is in support of previous studies suggesting decreased CTLA-4 function and increased incidence of autoimmune disease for this genotype. The 92-, 94-, and 100-bp alleles of CTLA-4 +642(AT) n occurred more often in African-American transplant recipients and were associated with decreased graft survival (p = 0.0001 and 0.007, respectively) but the independence of these variables could not be established. No associations with acute rejection or graft survival were found for CTLA-4 -318C/T or CD28 IVS3 +17T/C. The described associations between CTLA-4 gene polymorphisms and transplant outcomes provide the foundation for further investigations leading to genetic risk stratification for transplant recipients.

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Microsatellite alterations on human chromosome 11 in in situ and invasive breast cancer: A microdissection microsatellite analysis and correlation with p53, ER (estrogen receptor), and PR (progesterone receptor) protein immunoreactivity

Cited by 20 publications

References 24 publications

Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability

Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability

Clinicopathological and molecular analysis of endometrial carcinoma associated with tamoxifen

The Impact of Costimulatory Molecule Gene Polymorphisms on Clinical Outcomes in Liver Transplantation

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