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ABSTRACT: To investigate the aberrant promoter hypermethylation as a screening tool for cervical adenocarcinomas (CAs) and endometrial adenocarcinomas (EAs) in cervical scrapings.
A quantitative multiplex methylation-specific polymerase chain reaction approach was used to examine promoter methylation of 5 genes (APC, HIN-1, RAR-beta, RASSF1A and Twist) in biopsy-confirmed CA (n = 31) and EA (n = 27) residual, liquid-based cytology samples. The data of negative for intraepithelial lesions or malignancy and low-grade squamous intraepithelial lesions were used as controls.
Methylation levels of APC, RAR-beta, RASSF1A and Twist were significantly higher in CA than in control cervical samples. For EA, only the methylation levels of RASSF1A differed significantly from those of control. Receiver-operating characteristic analysis demonstrated that APC, RAR-beta and RASSF1A had the ability to distinguish CA/EA, CA and EA from control samples. In CA/EA and CA samples, the best 3-gene combination was RASSF1A/RAR-beta/APC. This 3-gene panel had a sensitivity of 87.0% for CA/EA and of 80.6% for CA and a specificity of 79.3% for both CA/EA and CA. In EA samples, RASSF1A showed the best performance in distinguishing EA from control. The estimated sensitivity of RASSF1A for detecting EA was 63.0%, and its specificity was 96.3%.
This feasibility study demonstrates that quantitative detection of aberrant DNA methylation in cervical scrapings may be a promising new diagnostic tool for the detection of CA and EA.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 08/2012; 34(4):195-203. · 0.41 Impact Factor
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ABSTRACT: Phyllodes tumors (PTs) of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. Matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are involved in several key aspects of tumoral growth, invasion, and metastasis, but little is known of their expression in PTs. The objective of this study was to assess the expression of MMPs and TIMPs in PTs and to determine their association with grade and clinical behavior of PTs. Eighty-two PTs (50 benign, 22 borderline, and 10 malignant) were studied. Automated immunohistochemical staining for MMP-1, -2, -7, -9, -11, -13, and -14 and TIMP-1, -2, and -3 was performed using tissue microarray blocks and the expression of MMPs and TIMPs was assessed in the stromal component. There were no significant differences in the expression of stromal MMPs and TIMPs in the 3 groups of PTs, except for MMP-14. There was a significant increase in stromal MMP-14 expression with increasing PT grade (P<0.01). The stromal MMP-14 expression in the borderline and malignant PTs was higher than that in benign PTs (P<0.05 and P<0.05, respectively). Furthermore, the expression of stromal MMP-14 was associated with a higher rate of recurrence (P<0.05). Our results show for the first time that stromal MMP-14 expression is associated with the grade and clinical behavior of PTs of the breast.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 05/2012; 20(3):298-303. · 1.63 Impact Factor
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ABSTRACT: To ascertain the hormonal receptor profiles of the epithelial and stromal components of phyllodes tumors (PTs) and determine their relationship with stromal proliferation.
Eighty-two PTs (50 benign, 22 borderline, and 10 malignant) were studied. Automated immunohistochemical staining for estrogen receptor (ER)-alpha and -beta, progesterone receptor (PR), androgen receptor (AR), and Ki-67 was performed using tissue microarray blocks, and their expression was assessed in both the stromal and epithelial components.
The epithelial component demonstrated the expression for ER-alpha (45.6%, 36 of 79), ER-beta (37.2%, 29 of 78), PR (91.1%, 72 of 79), and AR (10.1%, 8 of 79). The stromal component was positive for ER-beta (29.3%, 24 of 82) only. The epithelial expression of ER-beta was found to be significantly correlated with the epithelial expression of AR (r = 0.352, p = 0.002). No association was found between hormone receptor expression and PT tumor grade. Stromal Ki-67 expression was statistically correlated with epithelial ER-beta, epithelial AR, and stromal ER-beta expression.
Epithelial and stromal ER-beta and epithelial AR expression in PTs was correlated with the proliferative rate in the stromal component. Immunohistochemical examination of ER-beta and AR may have some impact on the postoperative management of patients with PTs.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 02/2012; 34(1):41-8. · 0.41 Impact Factor
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ABSTRACT: Promoter hypermethylation has been shown to be a common mechanism for inactivation of tumor suppressor genes in breast cancer. The aim of this study was to investigate the prevalence of Slit2 promoter hypermethylation in both the tumor and serum samples of breast cancer patients with ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IBC). The methylation status of Slit2 was investigated in 210 tissue samples (15 breast with no pathological findings, 26 DCIS, and 169 IBC samples) and 123 corresponding serum samples (15 breast with no pathological findings, 26 DCIS, and 82 IBC samples) using methylation-specific polymerase chain reaction. Immunohistochemical staining for Slit2 was also performed using tissue microarray blocks to determine whether Slit2 promoter hypermethylation correlated with loss of Slit2 expression. Slit2 promoter hypermethylation was not detected in breast tissue and serum samples from patients with no pathological findings. DCIS or IBC showed a statistically higher frequency of Slit2 promoter hypermethylation compared to breast with no pathological findings in both the tissue and serum samples; however, there were no statistically significant differences between DCIS and IBC samples. Similar Slit2 promoter hypermethylation patterns were seen in the tissue samples and corresponding serum specimens (p < 0.001). Slit2 promoter hypermethylation was associated with loss of Slit2 expression. These results suggest that Slit2 promoter hypermethylation appears to be responsible for functionally silencing Slit2 expression. Slit2 promoter hypermethylation may be considered as a possible serum marker for early detection of breast cancer.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 09/2011; 459(4):383-90. · 2.49 Impact Factor
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ABSTRACT: The aim of our study was to determine the value of a panel that consisted of one epithelial marker (MOC-31) and two mesothelial markers (D2-40 and calretinin) for distinguishing between reactive mesothelial cells (RMCs) and adenocarcinomas (ACs) in effusion fluids. A total of 118 cell block specimens from pleural and peritoneal effusions, including 88 ACs and 30 benign effusions with RMCs were stained with antibodies against MOC-31, D2-40, and calretinin. MOC-31 membranous activity was observed in all samples from ACs, regardless of the primary tumor site. All benign effusion samples with RMCs were negative for MOC-31. All benign effusion samples with RMCs exhibited membranous staining for D2-40, and one AC case had focal reactivity for D2-40. Almost all benign effusions reacted positively with calretinin. Staining was noted in both the cytoplasm and the nucleus in the majority of cases. Scattered tumor cells had weak calretinin positivity in two AC cases. Background RMCs in AC effusions were consistently positive for D2-40 and calretinin. In general, D2-40 identified more RMCs than calretinin. The staining combination of positive for MOC-31 and negative for D2-40 or calretinin were 100% specific and 99% sensitive for ACs. Our data suggest that immunohistochemical studies performed on cell blocks with MOC-31, D2-40, and calretinin were useful in the differentiation between ACs and RMCs. D2-40 was a more sensitive marker for RMCs than calretinin.
Diagnostic Cytopathology 03/2009; 37(4):258-61. · 1.16 Impact Factor
