Possible predictors of histopathological response to neoadjuvant chemoradiotherapy for rectal cancer

The response to neoadjuvant chemoradiotherapy (CRT) varies greatly in patients suffering from locally advanced rectal cancer. Our aim was to correlate the response to CRT with the pre-treatment expression of heat shock protein 90 (Hsp90), small heat shock protein 16.2 (sHsp 16.2), phospho-Akt (p-Akt), growth hormone-releasing hormone receptor (GHRH-R) and heme-binding protein 2 (SOUL) in order to try to identify one or more as a predictive marker.

Sixty-nine patients receiving combined CRT for locally advanced rectal cancer were examined retrospectively. Surgical resection was carried out 6-9 weeks following CRT. The histopathological response to neoadjuvant treatment was determined according to the modified Mandard score. Using immunohistochemistry, we investigated the relationship between the expression of the five cited proteins in the pre-operative samples as well as various clinical parameters and the histopathological regression of the tumors.

Thirty-one patients (48%) were good responders, and 33 patients (52%) were found to respond poorly to neoadjuvant therapy. Among patients undergoing surgery 7 weeks following CRT, there were significantly more good responders than among patients who underwent surgery sooner (63% vs. 37%). High levels of expression of GHRH-R and Hsp90 were shown to be significantly correlated with minor or absent histological regression.

GHRH-R and Hsp90 were found to be independent predictive factors of histopathological response to neoadjuvant RCT. Since GHRH-R antagonists and Hsp90 inhibitors are currently being tested as potential anticancer agents, our study implies the possible elaboration of an effective and individualized treatment of poor responders.