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. 2006 Nov 6;95(9):1244-9.
doi: 10.1038/sj.bjc.6603359. Epub 2006 Oct 10.

Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma

R Maruyama  1 , K Yamana, T Itoi, N Hara, V Bilim, T Nishiyama, K Takahashi, Y Tomita
Affiliations

Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma

R Maruyama et al. Br J Cancer. .

Abstract

Immunotherapy is the only available treatment for metastatic renal cell cancer (RCC), but the response rate is only about 20% and the treatment is occasionally associated with severe adverse effects. Thus, the selection of patients with a high susceptibility to immunotherapy is needed; however, there is no promising molecular marker that can predict the response to immunotherapy for RCC. This study was carried out to elucidate the potential role of apoptosis-related molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI) as predictors of the susceptibility of metastatic RCC to immunotherapy. Immunohistochemical examination of tumour tissues from 40 patients with metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy was performed. Patients with progressive disease (PD) after immunotherapy presented with decreased survival (P=0.006). Progressive disease correlated with higher PI in the primary lesion (P=0.0087). All primary tumours of CR or PR patients were negative for Bcl-2, whereas among NC+PD patients, 40.6% were positive for Bcl-2 (P=0.0373). Patients in whom the primary tumours were both Bcl-2- and Fas-negative showed significantly better responses to immunotherapy in comparison with the remaining group (P=0.0022). The Bcl-2 and Fas status of the primary lesion may become useful criteria for the selection of patients with metastatic RCC for immunotherapy.

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Figures

Figure 1
Figure 1
(A) Patient No. 8 chest CT shows mediastinal lymph nodes at diagnosis (arrrowheads). (B) Mediastinal lymph node swelling disappeared after immunotherapy (CR).
Figure 2
Figure 2
(A) Disease-specific survival of all cases according to Bcl-2 expression. (B) Disease-specific survival in Bcl-2-negative cases only according to the response to immunotherapy. (C) Disease-specific survival of all cases according to Fas expression. (D) Disease-specific survival in Fas-negative cases only according to the response to immunotherapy. (E) Comparison of disease-specific survival between CR+PR vs NC+PD. (F) Comparison of disease-specific survival between Bcl-2 and Fas-negative cases in CR+PR vs others.
Figure 3
Figure 3
Immunohistochemical staining of (A) Bcl-2 (No. 300), (B) Fas (No.84), (C) Ki-67 (No. 242). Scale bars represent 100 μm.
See this image and copyright information in PMC

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