Cellular distribution of human tissue kallikreins: immunohistochemical localization.

We have studied the immunohistochemical expression (IE) of eight non-tissue-specific human kallikreins (hKs) (hK5, 6, 7, 10, 11, 12, 13, and 14) in different normal tissues. The IE was always cytoplasmic, showing a characteristic pattern in some tissues. Comparison of the IE of all hKs studied in the different tissues revealed no major differences, suggesting that they share a common mode of regulation. Furthermore, hKs were immunohistochemically revealed in a variety of tissues, indicating that no protein is tissue-specific (except for hK2 and hK3, which have tissue-restricted expression). In general, our results correspond well with data from RT-PCR and ELISA assays. Glandular epithelia constitute the main kallikrein IE sites, and the staining in their secretions confirms that these proteases are secreted. A variety of other tissues express the proteins as well. We have also immunohistochemically evaluated all the above hKs in several malignant tissues. Tumors arising from tissues expressing kallikreins tested positive. Corresponding to the IE in normal glandular tissues, most hKs were expressed in adenocarcinomas. The prognostic value of several hKs was studied in series of prostate, renal cell, colon and urothelial carcinomas.

Prognostic implications of the immunohistochemical expression of human kallikreins 5, 6, 10 and 11 in renal cell carcinoma.

Human kallikreins 5, 6, 10 and 11 (hK5, 6, 10 and 11) are expressed by many normal tissues, and it has been suggested that they may represent candidate tumor-diagnostic or -prognostic markers. In patients with renal cell carcinoma (RCC), outcome is unpredictable despite the use of conventional prognostic factors. The aim of this study is to evaluate the immunohistochemical expression and the prognostic value of the above kallikreins in RCC. The study comprised 95 patients who underwent radical nephrectomy for RCC. The median follow-up period was 60 months (range 1-180 months). Fifty-seven RCC cases were immunostained for hK5, 70 for hK6, 70 for hK10 and 69 for hK11. The streptavidin-biotin-peroxidase method of immunostaining was performed using anti-hK5, anti-hK6, anti-hK10 and anti-hK11 monoclonal and polyclonal antibodies. The immunohistochemical expression of these kallikreins was correlated with tumor size, histological type, histological malignancy according to the Fuhrman four-grade scale, mitotic index, pathological stage and disease survival. For the statistical analysis, four grades were collapsed into two by which RCC cases were categorized as low malignant (LM) and high malignant (HM). In the normal renal parenchyma adjacent to the tumors, the renal tubular epithelium showed a cytoplasmic expression of all four kallikreins. In RCC, immunohistochemical expression was decreased: 33 of 57 cases (58%) were positive for hK5, 27 of 70 (39%) for hK6, 46 of 70 (66%) for hK10 and 32 of 69 (46%) for hK11. A statistically significant positive correlation was observed among the immunohistochemical expression of all kallikreins. HM-RCC expressed all kallikreins in a higher percentage of cases than LM-RCC, but statistically significant differences were only observed for hK6 and hK10 (55 vs. 27%, p = 0.016, and 79 vs. 56%, p = 0.044, respectively). hK6 and hK11 expression showed a positive correlation to pathological stage: hK6 with both Robson and TNM 2002 staging systems (p = 0.010 and p = 0.017, respectively), and hK11 only with the Robson staging system (p = 0.045). In both the Kaplan-Meier and the univariate Cox regression analyses, hK6 expression was negatively correlated with disease-specific survival (p = 0.05 and p = 0.038, respectively). In univariate analysis, nuclear grade, Robson stage and TNM stage also correlated with disease-specific survival. However, in the multivariate analysis, TNM stage was the only independent prognostic factor. In conclusion, although the immunohistochemical expression of hK5, hK6, hK10 and hK11 was downregulated in RCC, tumors of high grade and late stage expressed one or more of the above kallikreins in a higher percentage of cases, and hK6 may predict a poor disease outcome in RCC.