Cell-lineage-specific transcription factors are a group of regulatory proteins expressed in embryonic, differentiated, or neoplastic cells of the same lineage and represent a valuable repertoire of tissue-specific markers for the diagnosis of human tumors. Together with PAX2, PAX8 is a nephric-lineage transcription factor and is required for the establishment of renal-lineage cells and the formation of the kidney. In contrast to PAX2, little is known about the expression of PAX8 in adult kidney and renal tumors. In this study, we used immunohistochemistry to investigate the expression of PAX8 in adult human kidney and renal epithelial tumors. We report here that PAX8 was detected in renal epithelial cells in all segments of renal tubules from the proximal tubules to the renal papillae and in the parietal cells of Bowman's capsule in the adult kidney. PAX8 was also present in 98% of clear cell renal cell carcinomas (RCCs), 90% of papillary RCCs, and 95% of oncocytomas, similar to PAX2. In addition, PAX8 was found in 82% of chromophobe RCCs, 71% of sarcomatoid components of RCCs, and 100% (2/2) of renal medullary carcinomas. Overall, PAX8 was detected in 85% of metastatic renal tumors. Interestingly, expression of PAX8 was noted in some urothelial cells in the renal pelvis and ureters and B23% of urothelial carcinomas of the renal pelvis, but not in the urothelium or urothelial carcinomas of the urinary bladder; this probably underlines the different embryonic origins of urothelial cells in the upper and lower urinary tracts. As shown in this study, PAX8 is widely expressed in normal and neoplastic renal tissues. PAX8 may be a useful additional marker for renal epithelial tumors; however, its specificity and sensitivity await further investigation.
In explant livers with chronic hepatitis C (HCV-C) we have noted a distinctive histologic variant that we have termed steatohepatitic hepatocellular carcinoma (SH-HCC) with features resembling non-neoplastic steatohepatitis, including large droplet steatosis, ballooning of malignant hepatocytes, Mallory-Denk bodies, inflammation, and pericellular fibrosis. This study was undertaken to further describe the characteristics and prevalence of this histologic variant in HCV-C and any possible association with underlying risk factors for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We selected two 2-year periods (mid-2003 to mid-2005 and 2007 to 2008), from which selected explant livers with HCV-C and HCC were examined to determine the characteristics and frequency of SH-HCC. The underlying cirrhotic liver was also reassessed for steatosis and evidence of steatohepatitis. Clinical records were consulted for concomitant NAFLD and NASH risk factors. The SH-HCC variant was found in a total of 22 of 62 HCC cases (35.5%). Fourteen of the 22 patients with SH-HCC (63.6%) had at least one known risk factor for NAFLD/NASH including diabetes (6 of 22, 27.3%), obesity (6 of 22, 27.3%), hypertension (11 of 22, 50%), and hyperlipidemia (5 of 22, 27.8%). In 14 of the 22 cases (63.6%) of SH-HCC, the non-neoplastic liver showed changes of NAFLD/NASH superimposed on otherwise typical features of HCV-C. In conclusion, in our series of HCV-C explants, approximately one-third of HCCs show a distinctive histological variant termed SH-HCC. Underlying risk factors for NAFLD and for NASH were identified in 63.6% of our cases. Moreover, non-neoplastic tissue in HCV-C explants showed changes of NAFLD/NASH in 63.6% of cases. These results suggest a possible NAFLD/NASH pathway leading to SH-HCC in the setting of HCV-C which requires further investigation in the future.
PAX8 is a nuclear transcription factor with limited expression in normal and neoplastic tissues in a cell lineage-dependent manner. PAX8 has been detected in embryonic Müllerian ducts, human fallopian tubes, and ovarian carcinomas. However, little is known about its expression in other areas of the female genital tract. In this study, we used immunohistochemistry (IHC) to examine PAX8 expression in the normal uterine corpus and cervix, malignant tumors arising from these sites, and malignant effusions. We reported here that PAX8 was also detected in endometrial epithelial cells and endocervical glands, with a lower expression level in the latter, but not in the stromal cells of these areas. All endometrial carcinomas (N = 52) were positive for PAX8, whereas endocervical adenocarcinomas (N = 5) and uterine leiomyosarcomas (N = 3) were negative for PAX8. PAX8 was detected in 70% (22/31) and 68.8% (11/16) of metastatic carcinomas of the ovary and endometrium in serous effusions, respectively. No PAX8 was detected in carcinomas of nongynecologic origin or noncarcinomas (N = 71) in serous effusions except in one renal-cell carcinoma and one carcinoma of unknown primary in a woman. In addition, papillary serous carcinomas of the peritoneum (N = 10) were diffusely positive for PAX8, implying a Müllerian origin similar to malignant tumors in the female genital tract. Our findings suggest that PAX8 is an additional IHC marker for carcinomas of Müllerian origin hence we recommend including PAX8 for evaluation of malignant serous effusions in women, especially when tumors of Müllerian origin are in the differential diagnosis.
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