TY - JOUR
T1 - Impact of gene-specific germline pathogenic variants on presentation of endometrial cancer in Lynch syndrome
AU - Bogani, Giorgio
AU - Ricci, Maria Teresa
AU - Vitellaro, Marco
AU - Ditto, Antonino
AU - Chiappa, Valentina
AU - Raspagliesi, Francesco
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Objective Lynch syndrome is a risk factor for developing endometrial carcinoma. Our aim was to evaluate the impact of gene-specific germline pathogenic variants on clinical features of patients affected by endometrial cancer. Methods Patients with a diagnosis of endometrial cancer and with a germline pathogenic variant in mismatch repair genes were reviewed. Patients were classified on the basis of classes of risk according to the ESGO-ESGO-ESTRO (European Society of Medical Oncology/European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology) guidelines. One-way analysis of variance (ANOVA) and Kruskal-Wallis test were performed to compare three groups of continuous parametric and non-parametric variables, respectively. χ 2 test was used to analyze proportions. Results Overall, 68 patients with endometrial cancer and Lynch syndrome were evaluated. Ten (14.7%) patients were excluded because of absence of information about the gene involved in Lynch syndrome, thus leaving 58 (85.3%) patients available for the final analysis. MLH1, MSH2, and MSH6 pathogenic variants were observed in 19 (32.7%), 33 (56.9%), and six (10.3%) patients, respectively. Mean±SD age at endometrial cancer diagnosis was 51±6.4, 43.5±7.4, and 60.3±8.8 years (p=0.0002). Prevalence of non-endometrioid endometrial cancer was 15.7%, 24.2%, and 0% in the MLH1, MSH2, and MSH6 groups, respectively (p=0.345). According to the ESMO-ESGO-ESTRO classification, low, intermediate, and high risk endometrial cancer accounted for 47.3%, 10.5%, and 42.1% of the MLH1 group, 57.6%, 3%, and 39.4% of the MSH2 group, and 50%, 50%m and 0% of the MSH6 group (p=0.009). Conclusions Patients with MLH1 and MSH2 pathogenic variants are at a higher risk of early onset of endometrial cancer than patients with MSH6 pathogenic variants.
AB - Objective Lynch syndrome is a risk factor for developing endometrial carcinoma. Our aim was to evaluate the impact of gene-specific germline pathogenic variants on clinical features of patients affected by endometrial cancer. Methods Patients with a diagnosis of endometrial cancer and with a germline pathogenic variant in mismatch repair genes were reviewed. Patients were classified on the basis of classes of risk according to the ESGO-ESGO-ESTRO (European Society of Medical Oncology/European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology) guidelines. One-way analysis of variance (ANOVA) and Kruskal-Wallis test were performed to compare three groups of continuous parametric and non-parametric variables, respectively. χ 2 test was used to analyze proportions. Results Overall, 68 patients with endometrial cancer and Lynch syndrome were evaluated. Ten (14.7%) patients were excluded because of absence of information about the gene involved in Lynch syndrome, thus leaving 58 (85.3%) patients available for the final analysis. MLH1, MSH2, and MSH6 pathogenic variants were observed in 19 (32.7%), 33 (56.9%), and six (10.3%) patients, respectively. Mean±SD age at endometrial cancer diagnosis was 51±6.4, 43.5±7.4, and 60.3±8.8 years (p=0.0002). Prevalence of non-endometrioid endometrial cancer was 15.7%, 24.2%, and 0% in the MLH1, MSH2, and MSH6 groups, respectively (p=0.345). According to the ESMO-ESGO-ESTRO classification, low, intermediate, and high risk endometrial cancer accounted for 47.3%, 10.5%, and 42.1% of the MLH1 group, 57.6%, 3%, and 39.4% of the MSH2 group, and 50%, 50%m and 0% of the MSH6 group (p=0.009). Conclusions Patients with MLH1 and MSH2 pathogenic variants are at a higher risk of early onset of endometrial cancer than patients with MSH6 pathogenic variants.
KW - endometrial cancer
KW - lynch syndrome
KW - MLH1
KW - MSH2
KW - MSH6
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U2 - 10.1136/ijgc-2019-000277
DO - 10.1136/ijgc-2019-000277
M3 - Article
C2 - 30772826
AN - SCOPUS:85065790637
VL - 29
SP - 705
EP - 710
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
SN - 1048-891X
IS - 4
ER -