Most cited article - PubMed ID 21107846
Tubulocystic renal carcinoma: a clinical perspective
Chromophobe renal cell carcinoma (ChRCC) is typically composed of large leaf-like cells and smaller eosinophilic cells arranged in a solid-alveolar pattern. Eosinophilic, adenomatoid/pigmented, or neuroendocrine variants have also been described. We collected 10 cases of ChRCC with a distinct multicystic pattern out of 733 ChRCCs from our registry, and subsequently analyzed these by morphology, immunohistochemistry, and array comparative genomic hybridization. Of the 10 patients, 6 were males with an age range of 50-89 years (mean 68, median 69). Tumor size ranged between 1.2 and 20 cm (mean 5.32, median 3). Clinical follow-up was available for seven patients, ranging 1-19 years (mean 7.2, median 2.5). No aggressive behavior was documented. We observed two growth patterns, which were similar in all tumors: (1) variable-sized cysts, resembling multilocular cystic neoplasm of low malignant potential and (2) compressed cystic and tubular pattern with slit-like spaces. Raisinoid nuclei were consistently present while necrosis was absent in all cases. Half of the cases showed eosinophilic/oncocytic cytology, deposits of pigment (lipochrome) and microcalcifications. The other half was composed of pale or mixed cell populations. Immunostains for epithelial membrane antigen (EMA), CK7, OSCAR, CD117, parvalbumin, MIA, and Pax 8 were positive in all tumors while negative for vimentin, TFE3, CANH 9, HMB45, cathepsin K, and AMACR. Ki67 immunostain was positive in up to 1 % of neoplastic cells. Molecular genetic examination revealed multiple chromosomal losses in two fifths analyzable tumors, while three cases showed no chromosomal numerical aberrations. ChRCC are rarely arranged in a prominent multicystic pattern, which is probably an extreme form of the microcystic adenomatoid pigmented variant of ChRCC. The spectrum of tumors entering the differential diagnosis of ChRCC is quite different from that of conventional ChRCC. The immunophenotype of ChRCC is identical with that of conventional ChRCC. Chromosomal numerical aberration pattern was variable; no chromosomal numerical aberrations were found in three cases. All the cases in this series have shown an indolent and non-aggressive behavior.
- Keywords
- ArrayCGH, Chromophobe renal cell carcinoma, Immunohistochemistry, Kidney, Multicystic,
- MeSH
- Chromosome Aberrations MeSH
- Diagnosis, Differential MeSH
- Immunohistochemistry methods MeSH
- Carcinoma, Renal Cell diagnosis genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Mucin-1 genetics metabolism MeSH
- Biomarkers, Tumor analysis MeSH
- Kidney Neoplasms diagnosis genetics pathology MeSH
- Adenoma, Oxyphilic diagnosis genetics metabolism MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Comparative Genomic Hybridization methods MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Mucin-1 MeSH
- Biomarkers, Tumor MeSH
Generally, patients with renal cell carcinoma (RCC) are viewed as potential candidates for antiangiogenic targeted therapy. Tubulocystic RCC (TCRC) is a recently described entity which may behave aggressively, and the rationale for antiangiogenic therapy in this group of renal tumors has yet to be determined. Seven TCRCs and five non-tumor tissue samples from seven patients were subjected to relative expression analysis of mRNA levels of 16 genes involved in three angiogenic signal pathways: (1) VHL/HIF, (2) RTK/mitogen-activated protein kinase (MAPK), and (3) PI3K/Akt/mTOR. Two of them, pathways (2) and (3), are often targeted by antiangiogenic agents. We also determined the mutation and methylation status of the VHL gene. Finally, the levels of vascular endothelial growth factor A (VEGFA), HIF-1α, HIF-2α proteins, and phosphorylated mTOR protein were also determined. The comparison of tumor and control samples revealed no changes of mRNA levels of the following genes: VHL, HIF-1α, HIF-2α, PTEN, Akt2, Akt3, mTOR, VEGFA, KDR, HRas, C-Jun, EGFR, and FGF2. Significantly elevated mRNA level of TP53 was found, while the mRNA levels of FLT1 and C-FOS were reduced in tumor samples. No mutations or methylation in the VHL gene were found. Changes in levels of studied proteins VEGFA, HIF-1α, HIF-2α, and increased phosphorylation of mTOR protein were not found. Three studied angiogenic pathways (VHL/HIF, RTK/MAPK, and PI3K/Akt/mTOR) seem not to be upregulated in TCRC samples, so there appears to be no rationale for a general recommendation of antiangiogenic targeted therapeutic protocols for patients with these tumors.
- MeSH
- Molecular Targeted Therapy methods MeSH
- Adult MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit metabolism MeSH
- Phosphorylation MeSH
- Angiogenesis Inhibitors pharmacology therapeutic use MeSH
- Carcinoma, Renal Cell blood supply drug therapy metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Von Hippel-Lindau Tumor Suppressor Protein metabolism MeSH
- Kidney Neoplasms blood supply drug therapy metabolism MeSH
- Neovascularization, Pathologic drug therapy genetics MeSH
- Aged MeSH
- Signal Transduction drug effects genetics MeSH
- TOR Serine-Threonine Kinases metabolism MeSH
- Basic Helix-Loop-Helix Transcription Factors metabolism MeSH
- Vascular Endothelial Growth Factor A metabolism MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- endothelial PAS domain-containing protein 1 MeSH Browser
- Hypoxia-Inducible Factor 1, alpha Subunit MeSH
- HIF1A protein, human MeSH Browser
- Angiogenesis Inhibitors MeSH
- MTOR protein, human MeSH Browser
- Von Hippel-Lindau Tumor Suppressor Protein MeSH
- TOR Serine-Threonine Kinases MeSH
- Basic Helix-Loop-Helix Transcription Factors MeSH
- Vascular Endothelial Growth Factor A MeSH
- VEGFA protein, human MeSH Browser
- VHL protein, human MeSH Browser