IgA antibodies to the 27-kDa heat-shock protein in the genital tracts of women with gynecologic cancers

Abstract

Heat‐shock proteins promote cell survival under adverse environmental conditions. Synthesis of the 27‐kDa (HSP27), 70‐kDa (HSP70), and 90‐kDa (HSP90) heat‐shock proteins is increased in malignantly transformed cells and has been associated with tumor proliferation, metastasis, and resistance to chemotherapeutic agents. The increased expression of heat‐shock proteins and their association with tumor‐specific antigens may result in local immunity to the heat‐shock proteins. We examined the occurrence of IgA antibodies to HSP27, HSP70, and HSP90 in the lower genital tracts of women with possible gynecologic cancers. Cervical samples were obtained from 119 consecutive women being evaluated for a gynecologic malignancy or returning for a follow‐up examination following cancer treatment. Aliquots were tested for IgA anti‐heat‐shock protein antibodies by ELISA. Aliquots were also tested for IgG antibodies to HSP27 as well as for human papillomavirus. Anti‐HSP27 IgA was detected in 85.7% of 21 women with endometrial cancer tested prior to diagnosis and in 41.1% of 17 women tested after treatment. In women with ovarian cancer, 77.8% of 9 women tested prior to diagnosis and 75.0% of 24 women evaluated after treatment were anti‐HSP27 IgA‐positive. Of 6 women with cervical cancer tested prior to diagnosis, 5 were positive for this antibody. None of 25 women with benign diagnoses or 46 healthy women were cervical IgA anti‐HSP27‐positive (P < 0.0001). In contrast, anti‐HSP27 IgG was not associated with a gynecologic malignancy. HSP27 cervical antibodies were not associated with the presence of human papillomavirus. Cervical IgA antibodies to HSP90 were associated with ovarian cancer; antibodies to HSP70 were not cancer‐associated. We conclude that cervical IgA antibodies to HSP27 may be indicators of a gynecologic malignancy. Int. J. Cancer 87:824–828, 2000. © 2000 Wiley‐Liss, Inc.

Antibodies against heat shock proteins in environmental stresses and diseases: friend or foe?

“…Conroy et al (1998aConroy et al ( , 1998b showed that antibodies to Hsp27, Hsp70, and Hsp90 were detectable in patients with breast cancer and that anti-Hsp27 and anti-Hsp90 antibodies were detectable only in patients, not in controls; they suggested that the increased levels of antibodies to Hsp27 were correlated with an improved survival, whereas high levels of antibodies to Hsp90 were correlated with the reduced survival of these patients. Korneeva et al (2000) also reported that there was a common prevalence of anti-Hsp27 IgA (but not IgG) in the genital tract of women with endometrial and with ovarian cancer before and after treatment, but not in 25 women with benign diagnoses nor in 46 healthy women; moreover, in the same study, IgA antibodies to Hsp70 were not cancerspecific, but IgA to Hsp90 were present in one-third of patients with ovarian cancer. Thus, cervical IgA antibodies to Hsp27 may be indicators of gynecologic malignancy.…”

Application of Bayesian Modeling of Autologous Antibody Responses against Ovarian Tumor-Associated Antigens to Cancer Detection

“…11). Autoantibody to heat shock proteins (Hsp), notably Hsp27 and Hsp90 (23)(24)(25), has also been associated with ovarian cancer, and this may reflect the ability of certain Hsps, such as Hsp70, to bind and activate dendritic cells (26).…”

The distinctive role of small heat shock proteins in oncogenesis

“…This released HSP-27 acts locally, or leaks into serum, in each case modulating immune system response. αHSP--27 IgA antibody has been found in serum along with increased levels of immunizing HSP-27 suggesting that HSP-27 triggers immune response [26,63]. The level of this αHSP-27 antibody correlates with the survival of breast cancer patients suggesting that inactivation of extracellular HSP-27 is beneficial for a long-term outcome, possible due to diminished immunosuppression [63].…”

“…αHSP--27 IgA antibody has been found in serum along with increased levels of immunizing HSP-27 suggesting that HSP-27 triggers immune response [26,63]. The level of this αHSP-27 antibody correlates with the survival of breast cancer patients suggesting that inactivation of extracellular HSP-27 is beneficial for a long-term outcome, possible due to diminished immunosuppression [63]. However, there are also suggestions that HSP-27 can increase tumorgenecity of cancer cells by inhibit apoptosis of some immune system cells, indirectly boosting immune response [12,37,87].…”

“…Since the presence of sHSPs is detected also in non-malignant specimens, they cannot serve as specific tumor markers. Most prominently, HSP-27 has been reported in estrogen-dependent malignancies such as: ovarian cancer (vs. benign changes), breast and endometrial carcinoma, nasopharyngeal and gastric cancer [3,26,39,52,57,63,68,69,92,103]. The gastric mucosa expresses HSP-27 in a continuous fashion from low levels observed in normal tissue, through modest expression in dysplastic mucosa, to the highest in metaplastic tissues [57,92].…”