Expression of renal cell carcinoma-associated markers erythropoietin, CD10, and renal cell carcinoma marker in diffuse malignant mesothelioma and metastatic renal cell carcinoma.
ABSTRACT Metastatic renal cell carcinoma (MRCC) involving the thorax can be difficult to distinguish from diffuse malignant mesothelioma (DMM) using traditional morphologic approaches. Standard panels of immunohistochemical markers are of limited benefit.
To investigate several antibodies to renal cell carcinoma-associated proteins for differentiating MRCC from DMM.
One hundred DMMs and 20 MRCCs were evaluated for immunoexpression of erythropoietin. The same cases and an additional 45 DMMs were evaluated for CD10 and renal cell carcinoma marker (RCCMa) immunoreactivity.
Erythropoietin was expressed in 100% of DMMs and MRCCs. Staining for CD10 was observed in 54% of DMMs and 100% of MRCCs. RCCMa stained 26% of DMMs and 55% of MRCCs. Although erythropoietin staining was similarly strong and diffuse in both DMM and MRC, patterns of staining for RCCMa and CD10 differed between MRCC and DMM. Immunoreactivity was strong and diffuse for both RCCMa and CD10 in most MRCCs. Of CD10-positive DMMs, nearly half showed staining in less than 50% of tumor cells and about one fourth of positive cases exhibited only weak to moderately intense staining. Only half of RCCMa-positive DMMs showed staining in more than 49% of tumor cells and staining was only weak to moderately intense in most cases.
Given the overlap in the expression of renal cell carcinoma markers in MRCC and DMM, results with these markers must be interpreted cautiously and should be used in conjunction with mesothelium-associated markers. Differences in expression may potentially help distinguish MRCC from DMM inasmuch as strong and diffuse expression of RCCMa and CD10 supports a diagnosis of MRCC over DMM.
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ABSTRACT: Neoadjuvant chemotherapy followed by cytoreduction surgery has been used where an accurate cytologic or pathologic diagnosis is usually required before the initiation of neoadjuvant chemotherapy. However, it is difficult to make definitive diagnosis of presence of cancer cells, particularly gynecologic versus non-gynecologic origin, from those ascites specimens due to the absence of specific biomarkers of gynecologic cancers. In the present study, we evaluated if, in addition to the routine morphologic diagnosis, the biomarker PAX8 could be useful in recognition of ovarian epithelial cancer cells prior to the neoadjuvant chemotherapy. Two hundred and two cytology specimens including 120 pretreatment ovarian cancer samples, 60 benign controls, and 22 malignant non-gynecologic cases were studied. All cytology slides were morphologically reviewed in a blinded fashion without knowing corresponding pathology diagnosis, if present. A total of 168 cytology specimens with a cell block were stained with PAX8 and Calretinin. These included patients with potential for ovarian cancer neoadjuvant chemotherapy (n = 96), metastatic cancers (n = 22), and benign controls (n = 50). Among the 96 ascitic samples prior to neoadjuvant chemotherapy, 76 (79%) showing morphologic features consistent with cancers of ovarian primary were all PAX+/Calretinin-. The remaining 20 (21%) cases were positive for adenocarcinoma, but morphologically unable to be further classified. Among the 22 metastatic cancers into the pelvis, one case with PAX8+/Calretinin- represented a renal cell carcinoma and the remaining 21 PAX8-/Calretinin- metastatic cancers were either breast metastasis (n = 4) and the metastasis from gastrointestinal tract (n = 17). Among the 50 benign control pelvic washing cases, 5 PAX8+/Calretinin-cases represented endosalpingiosis (n = 4) and endometriosis (n = 1), 25 PAX8-/Calretinin + cases showed reactive mesothelial cells, and the remaining 20 specimens with PAX8-/Calretinin- phenotype typically contained inflammatory or blood cells without noticeable diagnostic epithelia. PAX8 identifies all Mullerian derived benign or malignant epithelia. When combining with Calretinin, PAX8 is a sensitive marker to diagnose the carcinomas of ovarian origin, which will be ideal to be used for those patients with a possible advanced ovarian cancer prior to receiving neoadjuvant chemotherapy.Journal of Hematology & Oncology 08/2013; 6(1):60. DOI:10.1186/1756-8722-6-60 · 4.93 Impact Factor
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ABSTRACT: One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive hematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma (RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial and sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream molecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression of solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays a critical role in the development and progression of tumours in general, it is of special significance in the case of RCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers, including RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because the rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in RCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current knowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are equivocal and insufficient to draw a definitive conclusion.BMC Cancer 01/2013; 13(1):14. DOI:10.1186/1471-2407-13-14 · 3.32 Impact Factor
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ABSTRACT: Effusions, especially peritoneal, are seen in less than 2% of patients with renal cell carcinoma (RCC). Since the tumor cells in RCC are bland and nondescript, the involvement of serous effusions is difficult to diagnose. An accurate recognition of malignant effusion and differentiation from reactive mesothelial cells is imperative. A 55-year-old male presented with gradually progressive ascites. Cytospin preparations from ascitic fluid showed reactive mesothelial cells admixed with few smooth-contoured clusters of cells with moderate cytoplasm, vesicular nuclei with prominent nucleolus. He had undergone nephrectomy for papillary RCC two years earlier. Another 36-year-old man underwent left nephrectomy for suspected RCC. Intra-operative ascitic fluid was sent for cytologic examination and showed numerous reactive mesothelial cells along with few clusters of cells with scant to moderate amount of cytoplasm, vesicular nucleus and a small nucleolus. Considering the histomorphology of the primary renal tumor in both cases, a cytologic diagnosis of malignant peritoneal effusion, morphologically compatible with RCC was rendered. RCC, due to its bland cytologic features, is easily overlooked in effusions. In a known patient, the cytopathologist must be extra vigilant to pick up the few cell clusters present in the fluid preparations and differentiate them from reactive mesothelial cells. A close inspection of the cytologic features and comparison with the histopathology of the primary tumor helps in making an accurate diagnosis.CytoJournal 04/2010; 7(1):4. DOI:10.4103/1742-6413.62256