OA: Pathological features and clinical behavior of Lynch syndrome-associated ovarian cancer (UK)

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The most common histological subtype in our cohort was endometrioid adenocarcinoma but high-grade serous tumors were also seen.

Historically, ovarian cancer has been categorized based on morphology into Type I and Type II disease [16], although modern genetic approaches call into question the utility of such an approach, favoring genetic categorization based on mutation status as it better predicts prognosis and treatment response [16], [17] and [18].

Highlights

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Lynch syndrome-associated ovarian cancer (LSAOC) is rare and difficult to study.

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This is the largest reported series of OC from proven Lynch syndrome carriers.

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Endometrioid OC was most common, followed by high grade serous, clear cell and mixed histology.

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Most LSAOC was detected at stage 1 and overall 5-year survival was excellent at 80%.

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Surveillance found 2 LSAOC; 3 more were diagnosed following surgery for screen-detected endometrial cancer.

In total 1047 proven mutation carriers are included in the database. Of these, 577 are women. Only those with a confirmed diagnosis of Lynch syndrome based on germline sequencing were included in this study. Fig. 1 outlines the numbers of patients included and excluded at each stage of stratification.

  The mean age of diagnosis was 51 years (range 24–70 years). Diagnosis In total, there were 17 MLH1, 28 MSH2 and 7 MSH6 proven mutation carriers. The mean age of LSAOC in MLH1 was 48 years, in MSH2 it was 52 years and in MSH6 the average was 53 years. There was no significant difference between age at diagnosis of LSAOC and mutated gene (p = 0.51 ANOVA), although numbers are small. Of the 36 women with complete datasets (Table 1), eight met the Bethesda criteria for diagnosis of Lynch syndrome; this constitutes just 22% of the cohort.of OC dated from 1956 to 2015.

 Synchronous endometrial cancer or atypical hyperplasia was seen in 9 women (25%).