Search

Thymidylate synthaseexpression is known to be higher in squamous cell carcinoma than in adenocarcinoma of the lung. It is thought that this is the reason for the poor efficacy of pemetrexed in squamous cell carcinoma. However, there is limited data on thymidylate synthaseexpression in adenosquamous carcinoma, a distinct subtype of lung cancer containing both squamous and glandular differentiation. Furthermore, molecular alterations like epidermal growth factor receptor and Kirsten rat sarcoma 2 viral oncogene homolog mutations, which are seen in adenocarcinomas, are not well understood in mixed histology tumors such as adenosquamous carcinoma. In our study, we sought to better characterize adenosquamous tumors of the lung. Using immunohistochemistry to evaluate thymidylate synthaseprotein levels, we found that the expression of thymidylate synthasein these mixed tumors roughly parallel that of squamous cell carcinoma, instead of falling in between squamous cell and adenocarcinoma. Of note, in adenosquamous samples, the expression of thymidylate synthasewas more closely correlated within the two components than would be expected by random chance alone. Also, we had a relatively high rate of epidermal growth factor receptor (11%) and Kirsten rat sarcoma 2 viral oncogene homolog (33%) mutations in these specimens, with the mutations showing convergence in both the glandular and squamous components upon microdissection. Our results indicate that adenosquamous carcinomas are not simple mixtures of their two histological components; they rather behave as their own entity, and it is important to further understand their behavior. Given the similarity of thymidylate synthaseexpression between squamous cell and adenosquamous carcinoma, and that thymidylate synthaseis the main target of pemetrexed, we extrapolate that pemetrexed may also have inferior clinical activity in adenosquamous carcinoma.

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, PAX8is 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 PAX8in adult kidney and renal tumors. In this study, we used immunohistochemistry to investigate the expression of PAX8in adult human kidney and renal epithelial tumors. We report here that PAX8was 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. PAX8was also present in 98% of clear cell renal cell carcinomas (RCCs), 90% of papillary RCCs, and 95% of oncocytomas, similar to PAX2. In addition, PAX8was found in 82% of chromophobe RCCs, 71% of sarcomatoid components of RCCs, and 100% (2/2) of renal medullary carcinomas. Overall, PAX8was detected in 85% of metastatic renal tumors. Interestingly, expression of PAX8was noted in some urothelial cells in the renal pelvis and ureters and ∼23% 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, PAX8is widely expressed in normal and neoplastic renal tissues. PAX8may be a useful additional marker for renal epithelial tumors; however, its specificity and sensitivity await further investigation.