J Gynecol Oncol.  2020 Nov;31(6):e78. 10.3802/jgo.2020.31.e78.

Kallikrein 5 overexpression is associated with poor prognosis in uterine cervical cancer

Affiliations
  • 1Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
  • 2Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 3Department of Pathology, Ilsan Paik Hospital, Inje University, Goyang, Korea
  • 4Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 5Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 6Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Abstract


Objective
Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining.
Methods
We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0–1+) (n=120 patients) and moderate/strong (2–3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors.
Results
Patients with KLK5 2–3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0–1+. With a median follow-up of 60.8 (interquartile range, 47.5–77.9) months, patients with KLK5 2–3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0–1+ group) and 59.4% (vs. 72.8% in the KLK5 0–1+ group), respectively (all p<0.05). KLK5 2–3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis.
Conclusions
KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.

Keyword

Uterine Cervical Cancer; Kallikreins; Radiation Therapy; Prognosis
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