Independent validation of the prognostic significance of invasion patterns in endocervical adenocarcinoma: Pattern A predicts excellent survival

Gynecol Oncol. 2018 Nov;151(2):196-201. doi: 10.1016/j.ygyno.2018.09.013. Epub 2018 Sep 24.

Abstract

Objective: Recently, the pattern of invasion in usual-type human papillomavirus-associated endocervical adenocarcinoma (AC) was put forward as a novel variable to select patients with favourable prognosis. Based on destructiveness of stromal invasion, three patterns were proposed: A - no destructive stromal invasion, B - focal destructive stromal invasion, and C - diffuse destructive stromal invasion. We aimed to independently validate the clinical significance of this classification-system in 82 AC patients, and explored associations between invasion pattern and somatic mutations.

Methods: All patients surgically treated for FIGO stage IB-IIA usual type AC (1990-2011, n = 82) were retrospectively reviewed and classified into pattern A, B or C. Additional immunohistochemical analyses were performed for p53, MSH6, and PMS2. Moreover, previously obtained data on somatic hotspot mutations in 13 relevant genes was integrated.

Results: Of 82 AC, 22% showed pattern A, 37% pattern B, and 41% pattern C. Significant differences were observed between invasion patterns and tumour size, depth of invasion (DOI), lymph-vascular invasion (LVI), and lymph-node metastasis. Significantly fewer mutations were present in tumours with pattern A morphology (p = 0.036). All pattern A patients survived (p = 0.002) without recurrent disease (p = 0.005). In multivariate regression analysis including tumour size, DOI, LVI, and lymph node metastasis, invasion pattern was a strong independent predictor for recurrence-free and disease-specific survival (HR 3.75, 95%CI 1.16-12.11, and HR 5.08, 95%CI 1.23-20.98, respectively).

Conclusions: We have independently validated the clinical significance of invasion patterns for usual type endocervical AC. Pattern A predicts excellent survival, and a clinical trial should prove safety of a more conservative treatment for these patients.

Keywords: Adenocarcinoma; Cervical cancer; Depth of invasion; Lymph vascular invasion; Pattern of invasion; Validation cohort.

Publication types

  • Validation Study

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adult
  • Female
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Mutation
  • Neoplasm Invasiveness
  • Prognosis
  • Retrospective Studies
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / mortality*
  • Uterine Cervical Neoplasms / pathology