Summary The expression of epidermal growth factor receptor (EGFR) was studied immunohistochemically in 234 cases of transitional cell bladder cancer. EGFR was overexpressed in 35% of cases and distinct nuclear localisation of EGFR positivity was found in 31% of the tumours. Overexpression was related to invasive growth, grade 2-3 histology, non-papillary type, DNA aneuploidy and high proliferation rate of cancer cells. The expressions of p53 and EGFR were interrelated, while expression of c-erbB-2 was independent of EGFR expression. Progression of superficial tumours, recurrence-free survival and survival were independently related to overexpression of EGFR in multivariate analysis. T category, S-phase fraction and non-papillary type included all the available prognostic information when the entire cohort was analysed by multivariate methods. The results show that overexpression of EGFR is related to several malignant features and prognosis in superficial bladder cancer. Moreover, the results suggest that overexpression of EGFR is usually a late event in bladder cancer development related to genetic instability rather than an early event in malignant transformation. Further studies are still needed to establish whether the direct measurement of cell proliferation or analysis of growth factor receptors and other oncoproteins gives more accurate prognostic information in bladder cancer.

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Summary The expression of retinoblastoma (Rb), c-Myc and Bcl-2 proteins was studied by immunohistochemical methods in 104 cases of renal adenocarcinoma. One tumour was completely negative for Rb protein and altered expression pattern was detected in 36% of cases. A low fraction of Rb-positive nuclei was related to high grade (P = 0.016) and high mitotic index (P = 0.012). Twenty-eight per cent of the tumours expressed c-Myc in cancer cell nuclei and 87% showed cytoplasmic positivity. Cytoplasmic expression of c-Myc was related to high grade (P= 0.002), while nuclear expression of c-Myc was related to small tumour diameter (P = 0.034), low T category (P = 0.04), low mitotic index (P = 0.019) and expression of c-ErbB-2 (P = 0.0007). Overexpression of c-myc predicted favourable outcome in MO tumours (P = 0.0157). Bcl-2 was expressed in 20% of tumours and it was related to small tumour size (P<0.0001), low T category (P<0.0001), lack of venous invasion (P= 0.008), node negativity (P = 0.015) and absence of metastasis (P = 0.017). In multivariate analysis the expression of Rb, Bcl-2 and c-Myc had no independent prognostic value over T category (P<0.001), mitotic index (P = 0.008) and combined nuclear grade (P = 0.056).

A series of 191 female breast carcinomas (with long-term follow-up) were analysed immunohistochemically (with a monoclonal MIB1 antibody) for Ki-67 (a proliferation marker) expression with special reference to well-established prognostic factors and patient survival. Expression of Ki-67 was directly related to the S-phase fraction (P < 0.0001), the volume-corrected mitotic index (P < 0.0001), histological grade (P < 0.0001), the apoptotic index (P < 0.0001), oestrogen and progesterose receptor content (P < 0.0001 for both) and p53 accumulation (P = 0.001). No correlation was found between Ki-67 expression and lymph node status (P = 0.25), metastasis at operation (n = 0.81) or tumour size (n = 0.38). The proliferation rate, as measured by image analysis of Ki-67 expression, predicted survival in the entire cohort (P = 0.001) and in axillary-lymph-node-negative (ANN) patients (P = 0.003). The difference in recurrence-free survival between the high- and low-expression groups was greatest in ANN tumours, 40% (P = 0.008). In axillary-lymph-node-positive tumours, the Ki-67 expression was not significantly related to recurrence-free survival (P = 0.723). The results of multivariate survival analysis showed that tumour size, axillary lymph node status, and mitotic index were independent prognostic factors in the entire series whereas, in ANN cases, tumour size and Ki-67 labelling were independent prognostic factors. These findings imply that Ki-67 expression could be an important prognostic determinant in breast cancer. Because of the evident loss of the predictive power of tumour size in the 1990s, the prognostic value of Ki-67 expression may even be accentuated in the currently diagnosed small breast carcinomas.

Summary A retrospective analysis of 321 gastric cancer patients was made to assess the prognostic value of TNM classification, tumour differentiation, Lauren classification, proliferative rate, inflammatory reaction and tumour invasion in vascular or neural structures of the gastric wall. The TNM classification showed the strongest correlation with survival in univariate and multivariate analyses (P<0.0001). The invasion in lymphatic or vascular system and Lauren classification were also independent prognosticators in multivariate analysis (P<0.05). In univariate analysis, the WHO-grade, the size and the location of the tumour and perinueral invasion were significant prognostic factors (P<0.01), as were the infiltration of lymphocytes and plasma cells in the tumour (P<0.05). On the other hand, the mitotic indices reflecting the proliferative activity of the tumour cells showed no significant correlation with the prognosis. The results indicate that the prognostic power of the TNM classification can be further increased by assessment of the above special histological features in gastric cancer.