Impact of hyperthermic intraperitoneal chemotherapy on Hsp27 protein expression in serum of patients with peritoneal carcinomatosis

Abstract

Despite the strong rationale for combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis, thermotolerance and chemoresistance might result from heat shock protein overexpression. The aim of the present study was thus to determine whether the heat shock protein 27 (Hsp27), a potential factor in resistance to treatment, could have a higher level in serum from patients under this combined therapy. Patients receiving CRS plus HIPEC for peritoneal carcinomatosis (group 1), patients with cancer or a history of cancer undergoing abdominal surgery (group 2), and patients without malignancies undergoing abdominal surgery (group 3) were included. Hsp27 serum levels were determined before and at different times following CRS and HIPEC using enzyme-linked immunosorbent assay. In group 1 (n = 25), the high Hsp27 levels, observed at the end of surgery compared with before (p < 0.0001), decreased during HIPEC, but remained significantly higher than before surgery (p < 0.0005). In groups 2 (n = 11) and 3 (n = 15), surgery did not significantly increase Hsp27 levels. A targeted molecular strategy, inhibiting Hsp27 expression in tumor tissue, could significantly reduce resistance to the combined CRS plus HIPEC treatment. This approach should be further assessed in a clinical phase I trial.

Fig. 1

Variations in Hsp27 serum levels in the preliminary study. Lines from bottom to top show the minimum, 25th percentile, median, 75th percentile, and maximum. Asterisk indicates the mean value

Fig. 2

Variations in Hsp27 serum levels in group 1 (patients receiving cytoreductive surgery plus HIPEC for PC); in group 2 (patients with cancer or a history of cancer undergoing abdominal surgery); and group 3 (patients with no malignancies undergoing abdominal surgery). Lines from bottom to top show the minimum, 25th percentile, median, 75th percentile, and maximum. Asterisk indicates the mean value

Fig. 3

Correlation between the increase in Hsp27 levels and surgery duration in group 1, comprising patients receiving CRS plus HIPEC for PC (one extreme value has been omitted)