Endometrial Cancer in Females under 45 years in Aotearoa New Zealand

Abstract

Introduction: Endometrial cancer is the most common gynaecological malignancy in New Zealand, and its incidence rate continues to increase. Among those affected, higher rates of endometrial cancer are seen in Māori and Pacific females as compared to non-Māori non-Pacific females. While the average age of endometrial cancer diagnosis is over 60 years, approximately 8% of endometrial cancers are diagnosed under the age of 45 in New Zealand. The rising number of young endometrial cancer patients is a dramatic change in the histological pattern of presentation and warrants an acute need for research in these patients. Aims: The key objectives of this study are to investigate: i) demographic and clinical characteristics of endometrial cancer patients in New Zealand ii) histopathological and molecular characteristics of a subset of endometrial cancer patients (under the age of 45 years) from Auckland, New Zealand. Methods: Females who were diagnosed with endometrial cancer between 1996 and 2019 were identified from New Zealand Cancer Registry. Annual age-standardised incidence and mortality rates were calculated for each ethnicity (Māori, Pacific, and non-Māori non-Pacific) in three age groups (<45, 45-64, and ≥65). In addition, we performed a local retrospective clinical review of endometrial cancer patients (aged under 45 years living in Auckland) to identify a cohort of 13 patients for genomic testing. Following patient consent, a comprehensive cancer gene panel (Trusight Oncology 500, TSO500) and immunohistochemistry of mismatch repair proteins and p53 were performed to determine their molecular and histopathological characteristics. Results: Endometrial cancer accounts for 85.50% of all uterine cancer diagnosed in New Zealand between 1996 and 2019. Age-standardised incidence rates increased in all females and significantly in the <45, 45-64, and ≥ 65 age groups (annual percentage changes: 5.44, 1.41, and 1.51, respectively). Pacific females were associated with the highest age-standardised incidence rate (45.3 cases per 100,000 females) which increased most rapidly in those diagnosed under the age of 45 years (annual percentage change: 10.52). The local subset of 13 Auckland endometrial cancer patients (under the age of 45 years) had an average BMI of 46.84 kg/m2. The genomic profiles of these females revealed a high frequency of PIK3CA, CTNNB1, and PTEN mutations in eight, six, and four participants respectively, and a co-occurrence of PIK3CA and CTNNB1 mutations was observed in five participants. Histopathologically, there were 12 tumours of p53 wild-type phenotype and one tumour of p53 mutated phenotype. A retained immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) was observed in 12 tumours whist one tumour had a MLH1/PMS2 loss of expression. In terms of defining endometrial cancer molecular subtypes, there was a complete concordance between TSO500 and ProMisE classifiers, κ = 1.00, p <0.001. Conclusions: Endometrial cancer remains the most common gynaecological cancer in New Zealand. Health inequalities are evident in endometrial cancer between age and ethnic groups. There is a trend to an earlier onset of the disease, particularly amongst Pacific and Māori ethnic groups, which may be associated with the rising rate of metabolic disease in New Zealand. The TSO500 targeted panel provides promising results in grouping endometrial cancer into molecular subtypes that could guide targeting therapy, however, issues of high costs, sample quality, and poor patient understanding of genomics testing remain to be addressed.