The overexpression of three growth factor receptors: epidermal growth factor receptor (EGFR), ERB B2 and ERB B3 was evaluated immunohistochemically in 77 malignant and 15 benign colorectal neoplasms considering clinicopathological variables (histological structure, grade of differentiation, tumor localization, clinical stage of the disease). The relationship between the coexpression of EGFR-related proteins in individual patients was also evaluated. EGFR expression was revealed in comparable percentages of colorectal adenoma and in adenocarcinoma cases (80% and 70%) while ERB B2 expression was detectable more frequently in adenoma than in adenocarcinoma cases (87% and 54%). The presence of ERB B3 was observed in a higher percentage of adenocarcinoma than adenoma cases (65% and 40%). There was no correlation between the expression of studied tyrosine kinase receptors and histological grade or Dukes’ clinical stage and localization (proximal or distal) of colorectal adenocarcinoma. The incidence of EGFR and ERB B2 expression was higher in tubulovillous (100% for both receptors) than in tubular adenomas (63% and 75%), while the ERB B3 receptor was revealed more frequently in tubular than in tubulovillous neoplasms (50% and 28%). These differences appeared to be statistically nonsignificant. The concomitant expression of two growth factor receptors was observed in a higher percentage of colorectal adenomas than adenocarcinomas, and the coexistence of three growth factors was revealed in comparable percentages in malignant and benign colorectal tumors. Our results support the promotional rather than direct transformational role for the EGFR supergene family in colorectal tumorigenesis. The frequently observed coexpression of more than one EGFR-related protein in colorectal neoplasms indicates the possible cooperation of these receptors in mitogenic signaling transduction, facilitating the development and maintenance of the malignant phenotype.

BACKGROUNDThe serum markers CA125, tissue polypeptide specific antigen (TPS), and soluble interleukin‐2 receptor alpha (sIL‐2Rα) concentrations were determined in sera, cyst, and ascitic fluids from patients with malignant and benign ovarian neoplasms.METHODSCA125, TPS, and sIL‐2Rα concentrations were measured in sera, cyst, and ascitic fluids by immunoassays in 67 patients with carcinoma and in 32 patients with benign ovarian neoplasms.RESULTSCA125, TPS, and sIL‐2Rα levels were elevated significantly in sera from patients who had ovarian carcinoma compared with patients who had benign neoplasms (P < 0.001). Patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage III–IV disease had significantly higher serum levels for the markers studied compared with patients who had FIGO Stage I–II disease (P < 0.001 for CA125; P = 0.02 for TPS and sIL‐2Rα). Concurrent measurement of CA125 and sIL‐2Rα in sera identified 100% of ovarian carcinomas in FIGO Stage I–II. All patients with carcinoma demonstrated markedly higher levels of CA125 and TPS for both cyst and ascites compared with corresponding sera (P < 0.001). The level of sIL‐2Rα was higher statistically in ascitic fluid compared with the level in serum (P < 0.001); however, its values in sera and cyst fluids were comparable. In ascitic fluid, the CA125 level was significantly higher in patients who had FIGO Stage III–IV disease compared with patients who had FIGO Stage I–II disease (P = 0.002), whereas such correlations were not found for TPS or sIL‐2Rα. In cyst fluids, the levels of all studied markers were independent of the FIGO stage. In cyst fluids from patients with benign ovarian neoplasms, TPS and sIL‐2Rα levels were significantly lower compared with the levels in patients with ovarian carcinoma (P < 0.001), whereas the values of CA125 were overlapping. CA125 and TPS concentrations were higher in cyst fluids compared with corresponding sera, whereas sIL‐2Rα levels were comparable and low in cyst fluids and in the circulation of patients with benign neoplasms.CONCLUSIONSIn patients with ovarian carcinoma, TPS and CA125 concentrations were significantly higher in the place of their generation compared with the concentrations in blood circulation. sIL‐2Rα values were higher in ascites compared with the values in corresponding sera, and its concentrations in sera and cyst fluids were comparable. The assessment of serum sIL‐2Rα levels showed potential complementary value to CA125 for the detection of ovarian carcinoma in early FIGO stages; however, a 9% false positive rate limited the significance of cumulative value for a combination of these circulating markers. Cancer 2002;95:1886–93. © 2002 American Cancer Society.DOI 10.1002/cncr.10917

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Human colon Cancer usually develops on a mucosa which has already undergone multiple steps of genetic change. These multiple steps create a field effect characterized by the presence of morphologically normal, but biologically altered epithelial cells. This aims of this study were to evaluate whether the expression of carcinoembryonic antigen (CEA) can act as a phenotypic marker of the field effect, and to map its topography in relation to the presence of colorectal adenocarcinoma. The expression of CEA was tested by immunohistochemistry on morphologically normal mucosa at 4 increasing distances from 14 autologous cases of colorectal adenocarcinoma. CEA expression in the normal mucosa was compared to the tumor. The results show that in the mucosa adjacent to the edge of the autologous tumor, CEA is expressed to the same level as displayed in the Carcinoma; there is a decrease in CEA expression in normal mucosa located at 1 cm or more from the edge of Carcinoma. Mucosa sampled at 5 and 10 cm from the tumor expresses CEA at the same low level as in mucosa of control subjects with no colorectal neoplasm. In conclusion, this study demonstrates a gradient of CEA expression in the peritumoral area, supporting the concept of field effect, and maps its extent. These data are relevant to the biology of human colorectal Cancer, and more practically, to the optimal location of surgical resection.

Our data support the finding that ovarian cancer patients release significant amounts of KLK5 into serum and ascitic fluid but KLK5 antigen is low in serum of patients with benign ovarian tumors. Increased serum and ascitic fluid KLK5 levels are associated with poor patient outcome, thus underlining the importance of KLK5 as a biomarker for early detection as well as for disease management in ovarian cancer.