BRIEF REPORT |
Correspondence to: Hinke A.B. Multhaupt, Dept. of Pathology, Pennsylvania Hospital, 800 Spruce Street, Philadelphia, PA 19107. E-mail: himult@pahosp.com
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Summary |
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Cytokeratins (CKs) are a group of 20 antigenically distinct intermediate filaments, generally confined to epithelia and their neoplasms. Immunostaining for CKs, in particular coordinate staining for CK7 and CK20, has become a useful tool in diagnostic pathology. Although studies defining CK distribution in neoplasms identify 07.7% of renal cell carcinomas (RCCs) positive for CK20, none has described the incidence of CK20 immunopositivity in renal oncocytomas (ROs). Distinction between RCC and RO may be difficult but this distinction is clinically significant, prompting us to establish the incidence of CK20 positivity in RO. We selected fifteen surgical cases of RO from our archives and studied their immunoreactivity for CKs including CK7 and CK20; 12/15 (80%) were positive for CK20, with variation in the number of cells staining. There was also variation in the distribution of CKs within the cells, including diffuse cytoplasmic, perinuclear, and a punctate or dot-like pattern. Such punctate staining corresponds to cytoplasmic balls of intermediate filaments and has been described with CAM 5.2 in RO and CK20 in Merkel cell carcinomas. Our findings suggest that CK20 immunohistochemistry is a useful tool for distinguishing RCCs from ROs. (J Histochem Cytochem 49:919920, 2001)
Key Words: cytokeratins, renal cell carcinoma, renal oncocytoma, immunohistochemistry
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Introduction |
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Immunohistochemical staining for intermediate filaments is widely used in the diagnosis of neoplasms whose origin is uncertain by routine light microscopy. One class of intermediate filaments are the cytokeratins (CKs), a group of 20 related yet antigenically distinct proteins that are generally confined to epithelia and neoplasms thereof (
Although studies describe an almost complete lack of CK20 positivity in RCC (
Fifteen cases of RO were selected from our files. Cases not definitively identified as oncocytomas were excluded. Tissue sections were formalin-fixed, paraffin-embedded, and stained with hematoxylineosin. All paraffin-embedded tissues were immunostained using the avidinbiotinperoxidase technique with diaminobenzidine as a chromogen, on an automated immunostainer (Ventana ES; Ventana Medical Systems). We used antibodies against the following antigens: cytokeratin 7 (clone K72, prediluted; protease digestion; Ventana); cytokeratin 20 (clone K5 20.8, prediluted; protease digestion; Ventana); cytokeratins 8 and 18 (clone CAM 5.2, prediluted; protease digestion; BectonDickinson, San Jose, CA); and vimentin (clone V9, diluted 1:80; Biogenex, San Ramon, CA). All slides were counterstained with hematoxylin, dehydrated, and mounted. Microwave heat epitope retrieval was performed in a low-pH citrate buffer. A representative case was selected for ultrastructural study. Fresh tissue was fixed in 2.5% glutaraldehyde, then osmicated and processed for conventional embedding in Epon 812. Ultrathin sections were mounted on copper grids and stained with uranyl acetate followed by lead citrate before examination in a Philips CM10 electron microscope.
A total of 12/15 (80%) of cases were positive for CK20, 12/15 (80%) for CK7, 15/15 (100%) for CAM5.2, and 4/15 (27%) for vimentin. Regarding coordinate expression, 9/15 (60%) were CK7+/CK20+, 3/15 (20%) CK7+/CK20-, 3/15 (20%) CK7-/CK20+, and 0/15 (0%) were CK7-/CK20-. The extent of staining with all three antikeratins varied by case, ranging from less than 10% to over 80% of cells positive. In cases staining for vimentin, greater than 50% of cells were positive.
A peculiar variation in distribution of keratins was noted in the cells, including diffuse cytoplasmic staining, perinuclear rings, and punctate or dot-like staining (Fig 1A). One, two, or all three patterns were identified in individual cases. Noted in some cases was a zonal staining quality, i.e., regions of tumor demonstrated diffuse cytoplasmic staining, with other distinct regions showing the dot-like or the perinuclear pattern, possibly representing a clonal phenomenon. Vimentin-positive cases always showed a diffuse cytoplasmic pattern. Dot-like positivity for CAM 5.2 has been previously described to occur in 73% of ROs but in 0% of RCCs, and therefore if present distinguishes between these lesions (
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Of the clear-cell, papillary, and chromophobe variants of RCC, the latter presents the greatest difficulty in diagnostic distinction from oncocytoma. The published series we have reviewed show from 0% to 7.7% of RCCs positive for CK20 (
Given the degree of CK20 positivity we have identified in RO and the low level of expression reported in RCC, we conclude that CK20 immunostaining is a useful diagnostic tool for distinguishing between these lesions.
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Footnotes |
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Presented in part at the Joint Meeting of the Histochemical Society and the International Society for Analytical and Molecular Morphology, Santa Fe, NM, February 27, 2001.
Received for publication December 8, 2000; accepted February 16, 2001.
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