TY - JOUR AB - Endometrial cancer is the most common gynecologic cancer in the developed world. The cell-adhesion protein E-cadherin acts as a tumor-suppressor protein and is down-regulated by the transcription factor Snail, whose expression was shown to be associated with estrogen receptor signaling. This study aimed to investigate the expression of E-cadherin, Snail, and estrogen-receptor alpha in 87 primary tumors and 26 metastases of endometroid endometrial carcinomas. Reduced E-cadherin immunoreactivity was seen in 44.8% of the primary tumors and 65.4% of the metastases with a statistical correlation to higher tumor grade (P=0.003) only in metastatic lesions. About 28.7% of primary tumor specimens showed a positive Snail immunoreactivity that was correlated with reduced estrogen-receptor alpha expression (P=0.047). Positive Snail immunoreactivity was also seen in 53.8% of the metastases where it was correlated with higher tumor grade (P=0.003) and abnormal E-cadherin expression (P=0.003). Interestingly, a Snail expressing endometrial carcinoma-cell line showed a higher migration potential than a variant of this cell line with low levels of Snail. Taken together, our data are in line with a proposed role for Snail in endometrial tumor progression. AU - Blechschmidt, K.* AU - Kremmer, E. AU - Hollweck, R.* AU - Mylonas, I.* AU - Höfler, H. AU - Kremer, M.* AU - Becker, K.F.* C1 - 4223 C2 - 25063 SP - 222-228 TI - The E-cadherin repressor snail plays a role in tumor progression of endometrioid adenocarcinomas. JO - Diagn. Mol. Pathol. VL - 16 IS - 4 PB - Lippincott Williams & Wilkins PY - 2007 SN - 1052-9551 ER - TY - JOUR AU - Koch, I.* AU - Slotta-Huspenina, J.* AU - Hollweck, R.* AU - Anastasov, N. AU - Höfler, H.* AU - Quintanilla-Martinez, L. AU - Fend, F.* C1 - 1909 C2 - 23921 SP - 149-156 TI - Real-time quantitative RT-PCR shows variable, assay-dependent sensitivity to formalin fixation: Implications for direct comparison of transcript levels in paraffin-embedded tissues. JO - Diagn. Mol. Pathol. VL - 15 PY - 2006 SN - 1052-9551 ER - TY - JOUR AB - Carcinoma of the breast is thought to evolve through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. Here lumpectomy specimens from five patients were studied, selected for the presence of ductal hyperplasia without atypia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Laser microdissection of tissue allowed precise sampling and direct correlation of phenotypic and genotypic changes. Analyses of the samples revealed an increasing mean number of chromosomal changes occurring with increasing histologic severity, and for the first time chromosomal abnormalities were demonstrated in ductal hyperplasia without atypia. Chromosomal changes found in each of the four histologic entities included gains on 10q, 12q, 16p, and 20q and loss on 13q. In ductal hyperplasia without atypia, gain on 20q as well as loss on 13q was detected with high frequency (four of five samples). Alterations identified in more than 50% of atypical ductal hyperplasia samples included gains on 3p, 8q, 15q, and 22q and loss on 16q. In ductal carcinoma in situ, gain of DNA on 1q and 17q and loss on 4q were additionally found, and in invasive ductal carcinoma, further gains on 6p, 10q, 11q13, and 17p were identified. The chromosomal alterations occurring in the different histopathologic lesions strongly suggest that these regions harbor tumor suppressor genes or oncogenes significant for the development of ductal carcinoma of the breast. AU - Aubele, M. AU - Cummings, M.C.* AU - Mattis, A.E.* AU - Zitzelsberger, H. AU - Walch, A.K. AU - Kremer, M.* AU - Höfler, H. AU - Werner, M.* C1 - 23358 C2 - 31122 SP - 14-19 TI - Accumulation of chromosomal imbalances from intraductal proliferative lesions to adjacent in situ and invasive ductal breast cancer. JO - Diagn. Mol. Pathol. VL - 9 IS - 1 PB - Lippincott Williams & Wilkins PY - 2000 SN - 1052-9551 ER - TY - JOUR AB - Tumor cells in abdominal lavage specimens from patients with gastric carcinoma strongly predict subsequent peritoneal metastasis and poor prognosis. Reverse transcription (RT)-polymerase chain reaction (PCR) detection of wild-type E-cadherin has been claimed to be superior to conventional cytology for the detection of patients who subsequently develop peritoneal metastases. The present study tested this hypothesis and determined whether or not the detection of mutated, tumor-specific E-cadherin messenger RNA in abdominal lavage specimens serve as a useful diagnostic tool. Preoperative lavage specimens from 52 patients with diffuse-type gastric carcinoma and from 5 patients with benign disease were analyzed by conventional cytology and by RT-PCR for amplification of E-cadherin. Tumor cells were detected by cytology in 8 (15.3%) of the 52 patients with gastric cancer. The E-cadherin was detected in all 57 samples by RT-PCR. Two of these had abnormal E-cadherin amplification products confirmed to be mutations by direct sequencing, which were identical in the primary tumors. These findings suggest that the detection of wild-type E-cadherin is not sufficiently tumor specific. Also, for diffuse gastric carcinomas with confirmed E-cadherin mutations, detection of mutant E-cadherin by RT-PCR is a potentially valuable method for tumor cell detection in lavage specimens. AU - Schuhmacher, C.* AU - Becker, K.-F. AU - Reich, U. AU - Schenk, U.* AU - Müller, J.* AU - Siewert, J.R.* AU - Höfler, H. C1 - 21181 C2 - 19227 SP - 66-70 TI - Rapid detection of mutated E-cadherin in peritoneal lavage specimens from patients with diffuse- type gastric carcinoma. JO - Diagn. Mol. Pathol. VL - 8 PY - 1999 SN - 1052-9551 ER - TY - JOUR AB - Accumulation of p53 protein resulting in levels detectable by immunohistochemistry (IHC) has been proposed as an indicator of mutation of the p53 gene. We have investigated a panel of 23 fresh-frozen breast cancers by IHC (PAb 1801), Southern and Northern blot analysis, and direct sequencing of the mutation hot spot regions (exons 5-8) of the p53 gene. Three tumors (13%) showed an intense nuclear staining in the majority of malignant cells, but only one of these showed a mutation of the p53 gene (codon 237, Arg to His). Furthermore, a mutation (5-bp deletion) was identified in a tumor that showed no p53 immunoreactivity. Our results indicate that accumulation of p53 protein, as detectable by IHC, is not a reliable indicator for p53 gene mutation in human breast cancer. AU - Lohmann, D. AU - Ruhri, C. AU - Schmitt, M. AU - Graeff, H. AU - Höfler, H. C1 - 20311 C2 - 13500 SP - 36-41 TI - Accumulation of p53 Protein as an Indicator for p53 Gene Mutation in Breast Cancer: Occurence of False-Positives and False-Negatives. JO - Diagn. Mol. Pathol. VL - 2 IS - 1 PY - 1993 SN - 1052-9551 ER - TY - JOUR AB - In basal cell carcinoma, release of proteolytic activity is implicated in extracellular matrix degradation and tumor infiltration. The stromelysin metalloproteinase family is a major candidate for the matrix proteolytic activity in infiltrative tumors. However, in murine models of basal cell carcinoma, neither stromelysin 1 nor 2 appears to play a role in tumor infiltration. We have analyzed the expression of the newly described stromelysin 3 in human basal cell carcinoma using Northern blot analysis and in situ hybridization. In 12 of 14 cases, levels of stromelysin 3 expression were more than tenfold above those observed in normal skin. In one of five cases of squamous cell carcinoma, stromelysin 3 expression was tenfold above levels seen in normal skin. Stromelysin 3 expression was either undetectable or extremely weak in all five cases of infiltrative malignant melanoma. In basal cell carcinoma, stromelysin 3 transcripts were localized by in situ hybridization to the stromal tissue immediately adjacent to basal cell carcinoma, the tumor cells themselves being negative. Therefore, expression of stromelysin 3 in stromal cells may be expected to play a significant role in destruction of the basal membrane zone and extracellular matrix in basal cell carcinoma invasion. AU - Wagner, S.N. AU - Ruhri, C. AU - Kunth, K. AU - Holecek, B.U. AU - Goos, M. AU - Höfler, H. AU - Atkinson, M.J. C1 - 20009 C2 - 13177 SP - 200-205 TI - Expression of Stromelysin 3 in the Stromal Elements of Human Basal Cell Carcinoma. JO - Diagn. Mol. Pathol. VL - 1 IS - 3 PY - 1992 SN - 1052-9551 ER -