Co-expression of CDX2 and MUC2 in gastric carcinomas: Correlations with clinico-pathological parameters and prognosis

AIM: To evaluate the role of CDX2 homeobox protein as a predictor for cancer progression and prognosis as well as its correlation with MUC2 expression. CDX2 represents a transcription factor for various intestinal genes (including MUC2) and thus an important regulator of intestinal differentiation, which could previously be identified in gastric carcinomas and intestinal metaplasia. METHODS: Formalin-fixed and paraffin-embedded tissues from 190 gastric carcinoma patients were stained with monodonal antibodies recognizing CDX2 and MUC2, respectively. Immunoreactivity was evaluated semiquantitatively and statistical analyses including x2 tests, uni- and multi-variate survival analyses were performed. RESULTS: CDX2 was mostly expressed in a nuclear or supranuclear pattern,whereas MUC2 showed an almost exclusive supranuclear reactivity.Both antigens were present in >80% of areas exhibiting intestinal metaplasia. An immunoreactivity in >5% of the tumor area was observed in 57% (CDX2) or in 21% (MUC2) of the carcinomas.The presence of both molecules did not correlate with WHO, Lauren and Goseki classification (with the exception of a significantly stronger MUC2 expression in mucinous tumors). CDX2 correlated with a lower pT and pN stage in the subgroups of intestinal and stage I cancers and was associated with MUC2 positivity.A prognostic impact of CDX2 or MUC2 was not observed. CONCLUSION: CDX2 and MUC2 play an important role in the differentiation of normal, inflamed, and neoplastic gastric tissues. According to our results, loss of CDX2 may represent a marker of tumor progression in early gastric cancer and carcinomas with an intestinal phenotype.

Liver tumor infiltrating lymphocytes: Comparison of hepatocellular and cholangiolar carcinoma

AIM: To investigate the role of tumor inf iltrating lym-phocytes (TIL) in primary hepatocellular and cholangio-lar carcinomas of the liver.METHODS: Immunohistochemical analysis was per-formed including antibodies to CD3, CD4, CD8, CD20, CD56 and TIA-1 in formalin-f ixed and paraff in-embed-ded tissue of 35 liver resection specimens of hepatocel-lular or cholangiocellular carcinomas. Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver interface.RESULTS: All hepatocellular carcinomas showed in-filtration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+ CD4+ T lymphocytes [164.3/10 high power f ields (HPF)] and in the tumor itself of CD8+ cells (54.9/10 HPF). Cholangiocarcinomas contained a heterogeneous amount of TIL, composed mainly of CD3+ T cells with a predominance of CD8+ cells in the tumor tissue (52.6/10 HPF) and of CD4+ cells in the interface region (223.1/10 HPF). CD56+ cells of the innate immune system were scarce. There was no significant difference between hepatocellular or cholangiolar carcinoma. No correlation with the clinicopathological data was seen. CONCLUSION: Liver TIL consists of intratumoral CD8+ T cells and peritumoral CD4+ T cells indepen-dent of histogenetic origin. Different functions of lym-phocytes in these regions seem possible.

Differential c-erbB-1 and c-erbB-2 mRNA expression in cancer of the pancreas compared with cancer of the papilla of Vater

AIM： We examined quantitative mRNA expression of growth factor receptors （c-erbB-1, c-erbB-2） and the anti-apoptosis gene survivin known to be regulated in pancreatic adenocarcinomas and compared the expression pattern with that in carcinomas of the papilla of Vater. METHODS： Quantitative real-time reverse transcriptase- PCR （QRT-PCR, Taqman^TM） was performed to analyze mRNA expression levels of c-erbB-1, c-erbB-2 and survivin in normal and corresponding tumor samples of 31 pancreatic adenocarcinomas and 8 cancers of the papilla of Vater. RESULTS： The overall median mRNA expression of survivin was significantly increased in both adenocarcinoma of the pancreas （P〈0.01） and papilla of Vater （P〈0.008） compared with uninvolved normal control tissue. In pancreatic cancer, expression of c-erbB-1 was significantly decreased compared with the normal pancreatic tissue （P〈0.03）, whereas in the cancer of the papilla of Vater expression of c-erbB-2 was significantly downregulated （P〈0.05） compared with the paired normal samples. Gene expression was not associated with tumor stage, differentiation or prognosis. CONCLUSION： The common anti-apoptosis gene survivin is overexpressed both in the cancer of the papilla of Vater and pancreas. In contrast, the growth factor receptor genes c-erbB-1 and c-erbB-2 are differentially regulated in both tumor entities adding further evidence that pancreatic cancer is biologically different from the cancer of papilla of Vater.

Cytochrome P450 levels are altered in patients with esophageal squamous-cell carcinoma

AIM： To investigate the role of cytochrome P450 （CYP） in the carcinogenesis of squamous-cell carcinoma （SCC） in human esophagus by determining expression patterns and protein levels of representative CYPs in esophageal tissue of patients with SCC and controls. METHODS： mRNA expression of CYP2E1, CYP2C, CYP3A4, and CYP3A5 was determined using RT-PCR in both normal and malignant esophageal tissues of patients with untreated esophageal SCC （/7 = 21） and in controls （n = 10）. Protein levels of CYP2E1, CYP2CS, CYP3A4, and CYP3A5 were measured by Western blot. RESULTS： Within the group of SCC patients, mRNA expression of CYP 3A4 and CYP2C was significantly lower in malignant tissue （-39% and -74%, respectively, P 〈 0.05） than in normal tissue. Similar results were found in CYP3A4 protein levels. Between groups, CYP3A4, CYP3A5, and CYP2C8 protein concentration was significantly higher in non-malignant tissue of SCC patients （4.8-, 2.9-, and 1.9-fold elevation, P 〈 0.05） than in controls. In contrast, CYP2E1 protein levels were significantly higher in controls than in SCC patients （＋46%, P 〈 0.05）. CONCLUSION： Significant differences exist in protein levels of certain CYPs in non-malignant esophageal tissue （e.g. CYP2CB, CYP3A4, CYP3A5, and CYP2E1） between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus.