乌鸦传媒

Although it is the most widespread gynecologic malignancy in industrialized countries, endometrial cancer often is diagnosed at an early stage and therefore has a generally favorable prognosis.^1,2 In most cases, surgery is the chosen mode of treatment.³ However, about 20% of patients with early stage endometrial cancer present with a poor prognosis regardless of the presence or absence of well-defined histologic risk factors.⁴

A recent study, led by Dr. Emanuele Perrone of Agostino Gemelli IRCCS University Hospital Foundation in Rome, Italy, assessed the clinical reproducibility and potential oncologic and prognostic value of a risk stratification scheme based solely on immunohistochemistry (IHC).⁴ Their overall conclusion: the system shows promise.

Retrospective IHC analyses were conducted in a series of 778 preoperative uterine-confined endometrial cancers, determining the presence/absence of MLH1, MSH2, MSH6, and PMS2 to define the mismatch repair (MMR)-stable or MMR-unstable phenotype, as well as the presence of p53 mutations and other molecular features.⁵

Overall, the p53-mutated cohort presented the worst clinicopathologic prognosis, the mismatch repair-unstable cohort an intermediate prognosis, and the mismatch repair-stable cohort the best prognosis.⁵ A correlation between IHC characteristics and FIGO staging was detected, with Stage IA tumors diagnosed in 62.1% of MMR-stable tumors vs 50.5% of MMR-unstable tumors and in 36.8% in the p53-mutated tumors.⁵ Stages II and III were generally twice the rate in the p53-mutation cohort (P<0.001), a finding that was confirmed after dividing the study population in early vs advanced stage disease (MMR-stable 18.4%, MMR-unstable 14.1%, p53-mutated 8.5%; P=0.004).⁵

Risk class stratification generally followed the same tendency as observed for stage differences, with low- and intermediate-risk endometrial cancers more predominant in the MMR-stable and MMR-unstable cohorts and the high-risk population mostly represented by those with p53-mutation positive disease (P<0.001).⁵ The patients with p53-mutated tumors also generally had more aggressive pathologic tumor characteristics, with lymph vascular invasion (P<0.001), deeper myometrial invasion (P=0.003), and greater dimension (P=0.003).⁵ In contrast, no differences were found in the rate of positive lymph nodes in the 3 cohorts.⁵

The hormonal receptor rate was profoundly different between the 3 groups, with 2+ and 3+ estrogen receptor and progesterone receptor positivity a unique characteristic of the MMR-stable and MMR-unstable cohorts, while the p53-mutation cohort generally had either negative or low hormonal receptor expression (P<0.001). No significant differences were found among the 3 cohorts in the proportion of adjuvant-treated patients or type of adjuvant treatment they received.⁵

These prognostic differences were confirmed by survival trends between the 3 subgroups in both 2-year disease-free survival (91.6%, 88.1%, and 56.4% for MMR-stable, MMR-unstable, and p53-mutated, respectively; P<0.0001) and 2-year overall survival (97.1%, 92.8%, and 81% for MMR-stable, MMR-unstable, and p53-mutated, respectively; P<0.00076).⁵ Multiple regression analysis in the MMR-stable group showed that high-risk classification influenced disease-free survival (P=0.017), and estrogen receptor status was a significant prognostic factor for both disease-free and overall survival (P<0.001 and P=0.003, respectively).⁵ There was no similar parameter impacting survival in the MMR-unstable or p53-mutated groups, with the exception of advanced-stage disease, which correlated with disease-free survival in both groups.⁵

鈥淭o the best of our knowledge, few studies [have] attempted to provide EC risk stratification based exclusively on IHC,鈥� the authors wrote. 鈥淲e presented a practical and highly reproducible IHC-based model to define a prognostic and histopathological risk stratification in a large, retrospective EC series [that] highly correlated with histopathological features and clinical outcomes.鈥�⁵ They noted that prospective validation of the proposed model is required before using the risk stratification scheme in clinical practice, but that it appears to be 鈥減erfectly in line with the growing need for a sustainable precision medicine approach in EC care.鈥�⁵

Published: July 29, 2022