PAX 8 is a transcription factor that is essential for embryonic development of the kidney, Mü llerian organs, and thyroid. It may also have a role in tumor development in these organs. The diagnostic utility of PAX 8 has not been comprehensively studied. Formalin-fixed, paraffin-embedded tissue samples for non-neoplastic tissues (n ¼ 1601), primary neoplasms (n ¼ 933), and metastatic neoplasms (n ¼ 496) were subjected to PAX 8 immunostain. In non-neoplastic tissues, PAX 8 was consistently noted in glomerular parietal epithelial cells, renal collecting ductal cells, atrophic renal tubular epithelial cells regardless of nephronic segments, and epithelial cells of the endocervix, endometrium, fallopian tube, seminal vesicle, epidydimis, thyroid, pancreatic islet cells, and lymphoid cells. PAX 8 was not seen in the rest of the tissue samples. In primary neoplasms, PAX 8 was expressed by 194 of 240 (89%) renal cell neoplasms, by 238 of 267 (89%) Mü llerian-type neoplasms, by 65 of 65 (100%) thyroid follicular cell neoplasms, by 8 of 8 (100%) nephrogenic adenomas, and by 17 of 17 (100%) lymphomas. Weak focal staining was noted in 5 of 12 (42%) cases of parathyroid hyperplasia/adenoma and in 6 of 17 (35%) well-differentiated neuroendocrine tumors of the pancreas. PAX 8 was not seen in other neoplasms. In metastatic neoplasms, PAX 8 was expressed by 90 of 102 (88%) metastatic renal cell carcinomas, by 57 of 63 metastatic Mü llerian tumors (90%), and by 6 of 6 metastatic papillary thyroid carcinomas (100%). There was also weak focal staining for 1 of 15 metastatic small cell carcinomas and for 1 of 9 metastatic well-differentiated neuroendocrine carcinomas. PAX 8 was not seen in other metastatic neoplasms. It can be successfully identified in routinely processed tissue samples, and its expression is mostly nuclear. PAX 8 expression in nonneoplastic mature tissues is limited to the organs, the embryonic development of which depends on this transcription factor. This tissue/cell-specific expression is maintained during both neoplastic transformation and metastasis. PAX 8 is a sensitive and specific marker for tumors of renal, Mü llerian, or thyroid origin in both primary and metastatic sites.

PAX-2 is a transcription factor that controls the development of the kidney, organs deriving from the mesonephric (Wolffian) duct, and those related to the Müllerian duct. Although PAX-2 is shown to be a sensitive marker for tumors derived from these organs, but whether it is specific, that is, whether other tumor types also express PAX-2, has not been systematically evaluated in either primary or metastatic tumors. Tissue sections from 937 normal or reactive tissue samples, 759 primary neoplasms, and 332 metastatic neoplasms were submitted to PAX-2 immunostain. Among the non-neoplastic tissue, PAX-2 was expressed in glomerular parietal epithelial cells, renal collecting duct cells, atrophic renal tubular cells, epithelial cells of ovarian surface, fallopian tube, endocervix, endometrium, seminal vesicle, and lymphocytes. Among the primary neoplasms, PAX-2 was noted in 104/122 (85%) of renal cell carcinoma, 31/95 carcinomas of Müllerian origin, 17/17 (100%) lymphomas, 4/4 (100%) nephrogenic adenomas, and 1/16 (6%) benign parathyroid tumors, but was negative in 477 other tumors. Among the metastatic tumors, PAX-2 was noted in 70/95 (74%) metastatic renal cell carcinomas, 14/20 (70%) metastatic tumors of Müllerian origin, 1/20 (5%) metastatic colon carcinoma of lymph nodes, 1/62 (2%) metastatic breast carcinoma of lymph nodes, but was not seen in the remaining 247 metastatic tumors. PAX-2 expression in non-neoplastic mature tissue is limited to the organs whose embryonic development depends on this transcription factor. PAX-2 is a sensitive and specific marker for tumors of renal or Müllerian origin in both primary and metastatic contexts.

The diagnosis of renal cell carcinoma (RCC) remains problematic, especially in the context of metastasis or small needle biopsy specimens. The renal cell carcinoma marker (RCCM) and kidney-specific cadherin (KSC) are considered specific markers for RCC but are expressed preferentially in specific subtypes of RCC of lower grades. This study was aimed at evaluating the usefulness of PAX-2 in the diagnosis of renal tumors and comparing it with that of RCCM and KSC. Immunostaining for PAX-2, RCCM, and KSC was performed on consecutive tissue sections of 130 renal tumors. PAX-2 was successfully detected in routine tissue specimens. Although PAX-2 seems to be more sensitive than RCCM and KSC, there is significant staining overlap in relation to histologic subtypes, justifying the use of all 3 markers, which helps detect the vast majority of renal neoplasms. PAX-2 seems to have a significant role in renal neogenesis and may represent a novel therapeutic target.

Context.—Seminal vesicle invasion by prostatic carcinoma is directly associated with tumor staging; verification is challenging when the tumor demonstrates cribriform or papillary growth patterns or there are back-to-back small-gland proliferations. P504S is overexpressed in prostatic carcinoma and high-grade prostatic intraepithelial neoplasia with cytoplasmic immunoreactivity. p63 has positive immunoreactivity in basal cell nuclei of benign prostatic glands. Many researchers use a combination of these antibodies and their different colors. Objective.—To evaluate the usefulness of a single-color P504S/p63 cocktail immunostain in verifying prostatic carcinoma within the seminal vesicle. Design.—Sections from 57 radical prostatectomy specimens of pathologic stage pT3b that contain seminal vesicle with prostatic carcinoma involvement were immunostained with primary antibodies against prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) and a cocktail of antibodies against P504S and p63. Results.—Prostatic carcinoma cells from all 57 cases were diffusely positive for P504S, PSA, and PAP with cytoplasmic staining and no p63 nuclear staining. Seminal vesicle epithelium from all 57 cases was negative for all 3 markers with distinct p63 nuclear staining of the basal cells. Benign prostatic tissue was positive for PSA and PAP, as well as for p63, but negative for P504S. Conclusions.—The P504S/p63 one-color cocktail is a practical and cost-effective stain to differentiate prostatic carcinoma that involves the seminal vesicle from seminal vesicle epithelium. It is superior to PSA or PAP when sections contain both seminal vesicle and benign glands because PSA and PAP cannot distinguish benign from malignant glands.

Chondroid syringoma is an uncommon epithelial and mesenchymal neoplasm of eccrine sweat glands. Most are benign, but some may exhibit aggressive behavior, including local recurrence and lymph node or distant metastases. Treatment is generally limited to radical surgical excision and possibly chemoradiation, although the latter is generally considered ineffective against these tumors. Histologic features of benign and malignant chondroid syringoma are similar, thus making morphology an unreliable marker for clinically aggressive behavior. Identification of biomarkers that predict clinical behavior would be potentially useful for selecting patients with malignant chondroid syringoma for targeted therapy. The purpose of this study was to investigate somatic mutations commonly involved in tumor pathways, and to determine if there is altered expression of tumor suppressors p16 and p53 in metastatic malignant versus benign chondroid syringoma. Five chondroid syringoma tissue samples were analyzed -2 aggressive and 3 benign. Immunostaining for tumor suppressor genes p16 and p53 was performed. Genomic DNA was isolated and genetic analysis was performed using a custom Sequenom MassArray. Chondroid syringomas with clinically aggressive behavior showed strong nuclear p16 expression in contrast to those with benign behavior. Both the malignant and benign chondroid syringomas demonstrated positive p53 expression with varying intensity. No somatic mutations were identified in any of the chondroid syringomas.