Association between expression of MMP-7 and MMP-9 and pelvic lymph node and para-aortic lymph node metastasis in early cervical cancer

J Obstet Gynaecol Res. 2018 Jul;44(7):1274-1283. doi: 10.1111/jog.13659. Epub 2018 May 16.

Abstract

Aims: To investigate the association of matrix metalloproteinase (MMP)-7 and MMP-9 with pelvic lymph node and para-aortic lymph node metastasis in early cervical cancer.

Methods: A total of 137 patients with early cervical cancer (Stage Ia2-IIa2) were recruited from the Department of Gynecology and Obstetrics, Tumor Hospital of Liaoning Province from January 2009 to May 2014. We evaluated the expression of MMP-7 and MMP-9 by immunohistochemistry and their association with the clinicopathological parameters such as pelvic, common iliac and para-aortic lymph node metastasis. Spearman correlation was performed to analyze the correlation between MMP-7 and MMP-9 in cervical cancer. Finally, the areas under the receiver operating characteristic curve (ROC) of MMP-7 and MMP-9 in pelvic lymph node metastasis were assessed.

Results: MMP-7 expression was significantly higher in patients with adenocarcinomas and adenosquamous carcinomas (P = 0.014), vascular cancer embolus (P = 0.041), pelvic lymph node metastasis (P = 0.000) and a higher level of Ki-67 (P = 0.000). MMP-9 expression was significantly associated with vascular cancer embolus (P = 0.003), depth of stromal invasion (P = 0.001), pelvic lymph node metastasis (P = 0.003), common iliac lymph node metastasis (P = 0.001) and para-aortic lymph nodes metastasis (P = 0.004). Coexpression of MMP-7 and MMP-9 was significantly associated with vascular cancer embolus (P < 0.001), higher expression of Ki-67 (P < 0.001) and pelvic lymph node metastasis (P < 0.001). Spearman correlation analysis indicated a positive correlation between MMP-7 and MMP-9 (r = 0.263, P = 0.002). Areas under the ROC of MMP-7 and MMP-9 were 0.707 and 0.646, respectively.

Conclusion: MMP-7 and MMP-9 expressions were associated with lymph node metastasis in patients with early cervical cancers, suggesting a positive correlation of MMP-7 and MMP-9 with invasive potential in early cervical cancers.

Keywords: MMP-7; MMP-9; cervical cancer; lymph node metastasis.

MeSH terms

  • Adult
  • Aged
  • Aorta / pathology
  • Female
  • Humans
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis / pathology
  • Matrix Metalloproteinase 7 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Pelvis / pathology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • MMP7 protein, human
  • Matrix Metalloproteinase 7
  • MMP9 protein, human
  • Matrix Metalloproteinase 9