Histopathologic analysis of angiogenic factors in localized renal cell carcinoma: The influence of neoadjuvant treatment

Abstract

Background: This study was conducted in order to clarify whether histopathologic analysis of factor thymidine phosphorylase (TP) and Factor VIII could be a useful predictor of postoperative recurrence in localized renal cell carcinoma. Therefore, the relationship between tumor infiltrated lymphocytes (TIL) and both TP and Factor VIII was studied. Method: Of the 71 patients who underwent surgery, 54 patients had no neoadjuvant therapy (group 1), 10 patients were preoperatively administered IFN-g (group 2), and the remaining seven patients preoperatively received IFN-g and transarterial embolization (group 3). Both TP and Factor VIII immunostaining were performed on formalin-fixed, paraffin-embedded archival tissue from 71 renal cell carcinoma specimens, while TIL immunostaining was performed on frozen sections. Positive immunostaining was quantitatively scored by a computer-assisted digital image analysis. For TIL, positive results were semiquantitatively scored. Results: A significant difference in the recurrence-free rate was recognized for Groups 1, 2 and 3 (P < 0.05). Therefore, the median TP-positive rate (PR), VIII-PR, number of microvessels and positive mean vascular area levels were investigated, between the recurrence cases (n = 6) and the recurrence-free cases (n = 11). Only the TP-PR levels showed a significant difference among them (P = 0.044). In regards to the neoadjuvant cases, a significant correlation was observed between both VIII-PR and CD4 (r = 0.815) as well as between VIII-PR and CD11b (r = 0.756). Conclusion:There was no clear evidence that the neoadjuvant treatment would increase the recurrence-free survival in patients with localized renal cell carcinoma. TP-PR might be a predictor of postoperative recurrence in patients with localized renal cell carcinoma.

Histopathological analysis of angiogenic factors in renal cell carcinoma

“…Our results also support the hypothesis that a low level of MVD is related to a poor prognosis in RCC. These results can be explained by the fact that a decreased MVD is associated with tumor fibrosis and the development of large vascular channels 26,27 …”

Cytoreductive nephrectomy for metastatic RCC in the era of targeted therapy

“…30 in addition to veGF, several other angiogenic factors are known to be secreted by rCC, including plateletderived growth factor (PDGF), basic fibroblast growth factor (FGF), transforming growth factor (tGF)β1, angio poietins and hepatocyte growth factor, but their exact relevance is unknown. 28,31,32 studies specifically designed to investigate proangiogenic factors and Cn have been hard to interpret in light of the fact that surgical therapy itself may confound results by inducing many of the same angiogenic factors.…”

Multimodal Approaches in the Management of Locally Advanced and Metastatic Renal Cell Carcinoma: Combining Surgery and Systemic Therapies to Improve Patient Outcome

“…There have been some nonrandomized, retrospective studies that have examined the role of preoperative tumor embolization as a neoadjuvant ''therapy'' before radical nephrectomy that have suggested a benefit for the embolization, but these findings await prospective validation (28,36). The benefit of embolization is hypothesized to be the release of tumor antigens as a consequence of the embolization, with resultant immunologic effects.…”