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Abstract Background Adrenal cortex oncocytic carcinoma (AOC) represents an exceptional pathological entity, since only 22 cases have been documented in the literature so far. Case presentation Our case concerns a 54-year-old man with past medical history of right adrenal excision with partial hepatectomy, due to an adrenocortical carcinoma. The patient was admitted in our hospital to undergo surgical resection of a left lung mass newly detected on chest Computed Tomography scan. The histological and immunohistochemical study revealed a metastatic AOC. Although the patient was given mitotane orally in adjuvant basis, he experienced relapse with multiple metastases in the thorax twice in the next year and was treated with consecutive resections. Two and a half years later, a right hip joint metastasis was found and concurrent chemoradiation was given. Finally, approximately five years post disease onset, the patient died due to massive metastatic disease. A thorough review of AOC and particularly all diagnostic difficulties are extensively stated. Conclusion Histological classification of adrenocortical oncocytic tumours has been so far a matter of debate. There is no officially established histological scoring system regarding these rare neoplasms and therefore many diagnostic difficulties occur for pathologists.

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. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In the past quarter century, several nomenclature systems for non-papillary urothelial lesions of the urinary bladder have been proposed. The 1998 World Health Organization and International Society of Urological Pathology (WHO/ISUP) classification recommended a four-tier system for the subdivision of flat intraepithelial lesions of the bladder. This classification was adopted by the WHO in 1999 and revised in 2004. In 2002, a more detailed classification of flat urothelial lesions was based on the Ancona International Consultation. Each of these lesions was defined with strict morphological criteria to provide more accurate information to urologists in managing patients. However, immunohistochemical markers including proliferation markers, cytoskeletal proteins, growth factors and their related receptors, cell adhesion molecules and oncogene proteins are increasingly being used in order to differentiate histologically similar lesions.

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., (Copyright 2006 S. Karger AG, Basel.)

Human kallikrein gene 14 (KLK14) is a recently discovered member of the tissue kallikrein family of secreted serine proteases, which includes hK3/prostate-specific antigen, the best cancer biomarker to date. Given that KLK14 is hormonally regulated, differentially expressed in endocrine-related cancers, and a prognostic marker for breast and ovarian cancer at the mRNA level, we hypothesize that its encoded protein, hK14, like hK3/prostate-specific antigen, may constitute a new biomarker for endocrine-related malignancies. The objective of this study was to generate immunological reagents for hK14, to develop an ELISA and immunohistochemical techniques to study its expression in normal and cancerous tissues and biological fluids. Recombinant hK14 was produced in Pichia pastoris, purified by affinity chromatography, and injected into mice and rabbits for polyclonal antibody generation. Using the mouse and rabbit antisera, a sandwich-type immunofluorometric ELISA and immunohistochemical methodologies were developed for hK14. The ELISA was sensitive (detection limit of 0.1 micro g/liter), specific for hK14, linear from 0 to 20 micro g/liter with between-run and within-run coefficients of variation of <10%. hK14 was quantified in human tissue extracts and biological fluids. Highest levels were observed in the breast, skin, prostate, seminal plasma, and amniotic fluid, with almost undetectable levels in normal serum. hK14 concentration was higher in 40% of ovarian cancer tissues compared with normal ovarian tissues. Serum hK14 levels were elevated in a proportion of patients with ovarian (65%) and breast (40%) cancers. Immunohistochemical analyses indicated strong cytoplasmic staining of hK14 by the epithelial cells of normal and malignant skin, ovary, breast, and testis. In conclusion, we report the first ELISA and immunohistochemical assays for hK14 and describe its distribution in tissues and biological fluids. Our preliminary data indicate that hK14 is a potential biomarker for breast and ovarian cancers.