Endometrial serous carcinoma: A retrospective review of histological features & their clinicopathological association with disease-free survival & overall survival

Abstract

Background & objectives: Endometrial serous carcinoma (ESC) is a high-grade epithelial neoplasm with increased risk for metastasis and recurrence. This study was aimed to assess various histomorphological features of ESC and their clinicopathological association with disease-free survival (DFS) and overall survival (OS).

Methods: A total of 205 slides (belonging to 120 patients) diagnosed as ESC from January 2009 to December 2015 were reviewed. Receiver operating characteristics (ROC) curves were established for the diagnostic performance of depth of invasion (DOI), tumour-free distance (TFD) to serosa and percentage myometrial invasion (MI%). OS and DFS were generated by Kaplan-Meier curves and prognostic significance by Cox regression analysis.

Results: The mean age at diagnosis was 61.8 yr and the mean tumour size was 4.01 cm. Majority of the females were multiparous (84%; n=94) and postmenopausal (89.2%; n=107). On histopathology, <50 per cent of MI was identified in 37 of the 104 (35%), while 62/104 (59.61%) patients had ≥50 per cent MI. Seven (6.7%) patients had full-thickness invasion with serosal involvement, while five (4.8%) patients had no microscopic MI (minimal uterine serous carcinoma). Information about MI was not available in 16 patients. TFD ≥7.0 mm, DOI ≥6.0 mm and MI% ≥40 were significant variables in univariate analyses for OS; however, on multivariate analysis; none of these turned out to be an independent predictor in terms of OS. For DFS, DOI (≥6.0 mm) and MI% (≥40%) showed a significant association, in univariate as well as multivariate analysis; however, TFD (≤7.0 mm) did not show any significant association with DFS. Follow up data were available in 111 of the 120 (92.5%) patients with a five-year OS and DFS of 22.2 and 17.2 per cent, respectively.

Interpretation & conclusions: Conventionally calculated DOI (less than or more than half thickness) did not show significance in the present study. Thus, calculating the actual myometrial DOI, MI% and TFD to serosa have the potential for contributing meaningfully to prognostication of ESC.

Keywords: DOI; ESC; Endometrium; MI%; myometrial invasion; prognosis; serous carcinoma; tumour-free distance.

Fig. 1

Figure showing pictographic representation of depth of invasion (DOI); tumour-free distance (TFD) and myometrial invasion percentage (MI%). a, depth of invasion; b, tumour-free distance from serosa; EMJ, endomyometrial junction.

Fig. 2

Histological pattern (A) papillary (H & E, x100); (B) glandular (H & E, x200); (C) solid (H & E, x200); (D) nuclear pleomorphism; (E) multinucleate giant cells and; (F) mitosis (black arrow; H & E, x400).

Fig. 3

(A and B) Endometrial intraepithelial carcinoma arising in an endometrial polyp (black arrow; H & E, x200); (C and D) strong expression of p53 protein in the neoplastic glands (red arrow). Weak staining pattern is noted in the benign glands (yellow arrow).

Fig. 4

(A) Diffuse and strong nuclear positivity for p53 protein (mutation type); (B) Absent staining of p53 protein (null type); (C) strong p53 expression in lymphatic emboli; (D) diffuse nuclear and cytoplasmic staining for p16.

Fig. 5

ROC curve of (A) tumour-free distance from serosa predicting overall survival of disease; (B) depth of invasion and absolute percentage myometrial invasion predicting survival of disease; Kaplan-Meier curve for (C) depth of invasion ≥6.0 mm vs. disease-free survival; (D) overall survival vs. depth of invasion ≥6.0 mm; (E) absolute percentage myometrial invasion ≥40% vs. disease-free survival; (F) overall survival vs. percentage myometrial invasion ≥40%; (G) tumour-free distance ≤7.0 mm vs. disease-free survival; (H) tumour-free distance ≤7.0 mm vs. overall survival.