The Morphologic and Molecular Heterogeneity of Papillary Renal Cell Carcinoma Type I May Impact Future Treatment Strategies
Jennifer L Dreiling, WM Linehan, Carlos Torres-Cabala, Maria J Merino. National Cancer Institute, Bethesda, MD
Background: Papillary renal cell carcinoma type 1, (PRCC I) is a category of hereditary and sporadic neoplasms characterized by the development of multiple tumors within the kidney. These tumors are recognized by the formation of papillary structures lined by small cuboidal cells with scant basophilic cytoplasm and indolent nuclei. In some cases, additional tumor morphologies such as clear cell and spindle cell patterns may be present. Whether morphologic heterogeneity occurs de novo or evolves as the tumor progresses and the significance of this heterogeneity and the molecular alterations are not known.
Design: Fifty cases of PRCC I were histologically evaluated for the presence of additional morphologic patterns besides typical papillary formation including: clear cell, tubular, solid, and spindle cell type. Expression patterns of CK7, CD10, MIB-1, and CD20 were evaluated by IHC. Areas of normal kidney parenchyma, papillary tumor, and heterogeneous morphologic variants were microdissected from FFPP tissue and the DNA extracted for determination of LOH in chromosomes 3p (VHL gene), 7q, 17p, and 1q. Trisomies of chromosomes 7 and 17 were evaluated by FISH or CISH.
Results: The most common morphologic change associated with PRCC I was that of clear cell (CC) type. This morphology could be seen focally or diffusely. The spindle cell morphology was encountered less frequently. Several cases showed a mixture of different morphologies, including the formation of thick papillary structures. Immunohistochemical staining for CK7 demonstrated decreased intensity in clear and spindle cell areas. Both the CC and non-CC phenotypes showed alterations in chromosome 7q. However, in 2 cases, LOH in 7q was only identified in the non-CC component. LOH in chromosome 3p and 1q was only demonstrated in CC areas. Trisomies of chromosomes 7 and 17 were identified in most cases.
Conclusions: Morphologic heterogeneity has been known to occur in tumors, but the associated genetic alterations and clinical implications remain under investigation. Our findings confirm the heterogeneity of PRCC I and the presence of different genetic alterations in the CC component that are not present in the non-CC areas. These changes suggest the possibility that identification of CC and/or other patterns may represent tumor progression or dedifferentiation. These findings may also be relevant in the establishment and development of new and effective therapeutic regimens.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 88, Tuesday Morning