Genetic, Immunohistochemical Factors Associated with Tumor Aggressiveness in Clear Cell RCC

By Kaitlyn D’Onofrio - Last Updated: May 7, 2021

A study published in Cancer Treatment and Research Communications sought to identify genetic alterations and immunohistochemical (IHC) factors associated with prognosis and tumor aggressiveness in clear cell renal cell carcinoma (RCC).

RCC is among the top 10 most common cancer diagnoses for men and women, the researchers noted, constituting 5% and 3%, respectively, of all diagnoses.

In the present study, 57 patients with ccRCC who underwent radical and partial nephrectomy between 2005 and 2011 and had at least 36 months of follow-up were evaluated. In the pathological study, IHC determination of associated biomarkers included Carbonic anhydrase IX (CAIX), CAM 5.2, CD10, c-erbB-2, EGFR, HIF-1a, Ki67, MDM2, PAX-2 y 8, p53, survivin, and VEGFR 1 and 2. Multiplex ligation-dependent probe amplification (MLPA) was utilized to perform genetic analysis. Chi-square, Kruskal-Wallis, and multivariate analysis were all used to evaluate IHC, and multivariate logistic regression (normal/deletion-duplication) was implemented for the genetic analysis.

The proportion of pathologic stage (pT) was: pT1, 61.8%; pT2, 32.7%; and pT3-T4, 5.4%. Overall, 16.3% were nodal (N) stage 1 or 2, and 19.3% had metastasis.

According to the researchers, 23.6% of patients had recurrent disease, largely due to distance (83.3%); 27.3% of patients died. Factors associated with a poorer Fuhrman grade were CAIX (P=0.035) and tumor size (P=0.001). Risks of the following outcomes were associated with deletion-duplication of genes:

  • death (APC, Bcl-2, and CDKN2A by 11, 7, and 4, respectively; SMAD4 reduced the probability by 88%)
  • tumor recurrence (CDKN2A by 15-fold; VHL reduced the probability by 87%)
  • pT >2 (CCND2, MDM2, and WT1 multiplied by 6, 7, and 9, respectively)
  • risk of N+ (CDK4 and EBF1 by 13); distant metastases (BRCA2 and DLEU1 by 5)
  • Fuhrman grade ?3 (BRCA1, BRCA2, and p53 by 40, 75, and 34, respectively; FHIT reduced by 96%)

Deletion-duplication of CDK4 increased survival by 13, and DCC by 16; both DLEU1 and RUNX1 decreased survival time by 80%.

“CAIX and tumor size are associated with increased aggressiveness. The mutations to level 5q, 9p, 11p, 12, 13q, 17, 18q and 21q are associated with more aggressive tumors and with worse survival rate,” the study authors concluded.