ABSTRACT
Purpose To compare the difference of Notch1 methylation in the breast cancer and hyperplastic lesions tissue from Uyghur in Xinjiang. Methods The methylation level of Notch1 gene in Uyghur breast tissues including usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma(IDC) were detected by MALDI-TOF-MS technique. The association of the methylation level with clinical pathological characteristics of patients was analyzed. The expression of Notch 1 protein was detected by immunohistochemistry. The relationship between the methylation status and expression was assay. Results The methylation rate of Notch l gene in UDH, ADH, DCIS, and IDC group was gradually decreased (P＜0.05). The 9 CpG sites methylation level of 13 CpG sites are statistically lower in cancer tissues (P＜0.05). The hypomethylation are accompanied with low differentiation, lymph node metastasis and high stage of TNM (P＜0.05). The lower DNA methylation is negatively correlated with the expression of Notch l (P＜0.05). Conclusion There was a differences of the expression and methylation rate of Notch 1 between breast cancer and hyperplastic lesions tissue, and its biological significances needs to be further studied.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the relevance between the promoter methylation status of Notch1 gene and the invasive ductal carcinoma and ductal hyperplastic lesions of the breast.</p><p><b>METHODS</b>Methylation status of Notch1 gene in human breast invasive ductal carcinoma (IDC, n = 89), ductal carcinoma in situ (DCIS, n = 20), atypical ductal hyperplasia (ADH, n = 11) and usual ductal hyperplasia (UDH, n = 20) were quantitatively evaluated by MALDI-TOF MS. The expression of Notch1 protein was detected by immunohistochemical stain (SP method).</p><p><b>RESULTS</b>Positive expression rates of Notch1 protein in IDC and DCIS were 91.0% (81/89) and 75.0% (15/20), respectively, which were significantly higher than those of ADH (4/11) and UDH (30.0%, 6/20;P < 0.05). Notch1 protein expression was correlated significantly with lymph node metastasis, pathological grades and TNM stages of IDC. The mean methylation levels of Notch1 gene at CpG_3, CpG_4.5 and CpG_8 significantly decreased in IDC group compared with those of DCIS, ADH and UDH groups (P < 0.0083). In breast carcinomas, the mean methylation rates of Notch1 gene at CpG_4.5, CpG_10.11, and CpG_14.15.16 loci in cases with axillary node metastasis were significantly lower than those without axillary node metastasis (P < 0.05); and the methylation rates at CpG_14.15.16 and CpG_18 loci in stage Iwere lower than that in stage II, further lower than that in stage III (P < 0.05); and that in CpG_1.2, CpG_12.13 loci in grade I (highly-differentiated group) were higher than that in grade II (moderate-differentiated group) and grade III (poorly-differentiated group) (P < 0.05); and the methylation rates at CpG_3, CpG_8 and CpG_14.15.16 loci in ER(+) PR(+) HER2(-) group were lower than that in ER(-) PR(-) HER2(+) group (P < 0.05).</p><p><b>CONCLUSIONS</b>There is an overall hypomethylation of Notch1 gene in breast invasive ductal carcinomas with corresponding over-expression of Notch1 protein. This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notch1, and this change may have important significance in breast tumorigenesis and the development. Specific hypomethylation at CpG_3, CpG_ 4.5 and CpG_8 loci of Notch1 gene may play a role in the pathogenesis of breast carcinoma, suggesting the progression and/or malignant transformation from benign glandular lesions of the breast.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Young Adult , Breast , Pathology , Breast Neoplasms , Genetics , Metabolism , Pathology , Carcinoma, Ductal, Breast , Genetics , Metabolism , Pathology , Carcinoma, Intraductal, Noninfiltrating , Genetics , Metabolism , Pathology , CpG Islands , Genetics , DNA Methylation , DNA, Neoplasm , Genetics , Disease Progression , Hyperplasia , Lymphatic Metastasis , Neoplasm Staging , Precancerous Conditions , Genetics , Metabolism , Pathology , Promoter Regions, Genetic , Receptor, Notch1 , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To study the clinicopathologic features and immunophenotype of renal cell carcinomas, and to discuss their diagnostic value.</p><p><b>METHODS</b>The clinicopathologic features of 114 cases of renal cell carcinoma were reviewed and categorized on the basis of 2004 WHO classification. Immunohistochemical study for a panel of antibodies (including CK, CD10, vimentin, CD117, AMACR, CK7 and TFE3) was carried out. The follow-up data, if available, were also analyzed.</p><p><b>RESULTS</b>The cases were reclassified into 5 subtypes, including 77 cases (67.5%) of clear cell carcinoma (CCRCC), 11 cases (9.6%) of papillary renal cell carcinoma (PRCC), 14 cases (12.3%) of chromophobe renal cell carcinoma (chrRCC), 10 cases (8.8%) of renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions (Xp11.2RCC) and 2 cases (1.8%) of unclassified renal cell carcinoma (unRCC). Immunohistochemical study showed that the expression rates of CK, CD10 and vimentin in CCRCC were 93.5% (72/77), 93.5% (72/77) and 75.3% (58/77), respectively. On the other hand, all the 11 cases of PRCC studied were positive for AMACR. The expression rate of CD117 in chrRCC was 78.5% (11/14). In the 10 cases of Xp11.2 RCC studied, the expression rates of TFE3, AMACR, CD10 and CK were 100% (10/10), 100% (10/10), 90% (9/10) and 70% (7/10), respectively.</p><p><b>CONCLUSIONS</b>The various subtypes of renal cell carcinomas are heterogeneous in histologic appearance and demonstrate distinctive immunophenotype. The expressions of CD10, vimentin, CD117, AMACR, CK7 and TFE3 are helpful in the differential diagnosis.</p>