In Italy, endometrial cancer ranks third among all female cancers in women aged 50-69 years. The Cancer Genome Atlas Research Network has defined the molecular stratification of endometrial cancer into four different molecular groups: POLE-mutant in 7% of women with this neoplasm, MMRd (mismatch repair deficient) in 28%, p53 abnormal in 26% and NSMP (no specific molecular profile) in 39% of endometrial cancers. From retrospective clinical trials carried out in the past, it has been possible to draw information on the prognosis of these molecular groups and their clinicopathological features. At the moment, this information has not yet been analysed prospectively. The purpose of the present study is to evaluate the clinicopathological features of a cohort of patients with endometrial cancer and known molecular data in order to establish their association in a real-world monocentric study. 70 patients with endometrial cancer and known molecular data were included in the study, who were referred for new diagnosis by the Istituto Oncologico Veneto in Padua and the Clinica Ginecologica of the Hospital – University of Padua in the period 2021-2022. The association between molecular phenotype and clinicopathological features (histology, FIGO stage, grading and lymphovascular invasion) was measured by Pearson’s chi-square test. In addition, a multivariate regression analysis was conducted to assess the impact of molecular phenotype on disease stage at diagnosis. Of the 70 patients examined, 10% (n = 7) belonged to the POLE mutant molecular group, 30% (n = 21) to the MMRd group, 20% (n = 14) to the p53 abnormal group and 39% (n = 27) to the NSMP group. Regarding the association between clinicopathological features and molecular phenotype, few correlations were statistically significant: in particular, in the p53 abnormal group, serous histology and high grading; in the NSMP group, endometrioid histology, low grading and absent/focal lymphovascular invasion. Analysis to assess the impact of molecular phenotype on disease stage was not statistically significant. For the first time after the introduction of molecular characterisation into clinical practice, the clinicopathological features of endometrial carcinomas were analysed in a real-world study. Only serous histology and high grading for the p53 abnormal molecular group and endometrioid histology, low grading and focal/absent lymphovascular invasion for the NSMP group proved to be significantly correlated with the molecular phenotype, consistent with literature data. The analysis assessing the impact of molecular phenotype on disease stage was not statistically significant. The limitation of the study is certainly the limited number of patients recruited, due to the fact that the routine molecular determination of endometrial cancer has recently been introduced. Furthermore, the short follow up did not allow real life evaluation of the prognostic impact of the molecular phenotype, so that in the future it would be desirable to expand the case series and update the data with a congruous follow up.
In Italia, il tumore dell’endometrio è la terza neoplasia per incidenza tra le donne nella fascia d’età 50-69 anni. Il Cancer Genome Atlas Research Network ha definito quattro gruppi molecolari di tumore dell’endometrio: POLE mutant presente nel 7% delle donne con questa neoplasia, MMRd (mismatch repair deficient) presente nel 28%, p53 abnormal nel 26% e NSMP (no specific molecular profile) presente nel 39% dei casi. In maniera retrospettiva dai trial clinici svolti in passato è stato possibile trarre informazioni in merito alla prognosi di questi gruppi molecolari e alle caratteristiche clinico-patologiche. Ad oggi, tali informazioni non sono ancora state analizzate in maniera prospettica. Lo scopo del presente studio è la valutazione delle caratteristiche clinico-patologiche di una coorte di pazienti con tumore dell’endometrio in relazione al fenotipo molecolare a cui appartengono, per stabilire una loro associazione in una casistica monocentrica real-world. Nello studio sono state incluse 70 pazienti con tumore dell’endometrio e noto dato molecolare, prese in carico per nuova diagnosi all’Istituto Oncologico Veneto di Padova e nella Clinica Ginecologica dell’Azienda Ospedale – Università di Padova nel periodo 2021-2022. L’associazione tra il fenotipo molecolare e le caratteristiche clinico-patologiche (istologia, stadio FIGO, grading e invasione linfo-vascolare) è stata misurata tramite il test del chi-quadrato di Pearson. È stata, inoltre, condotta un’analisi di regressione multivariata per la valutazione dell’impatto del fenotipo molecolare sullo stadio di malattia alla diagnosi. Delle 70 pazienti prese in esame, il 10% (n = 7) apparteneva al gruppo molecolare POLE mutant, il 30% (n = 21) al gruppo MMRd, il 20% (n = 14) al gruppo p53 abnormal e il 39% (n = 27) al gruppo NSMP. Dallo studio di associazione tra caratteristiche clinico-patologiche e fenotipo molecolare, solo alcune relazioni sono risultate statisticamente significative: in particolare, nel gruppo molecolare p53 abnormal, l’istologia sierosa e il grading elevato; nel gruppo molecolare NSMP, l’istologia endometrioide, il basso grado e l’invasione linfo-vascolare assente/focale. L’analisi per la valutazione dell’impatto del fenotipo molecolare sullo stadio di malattia non è risultata statisticamente significativa. Per la prima volta dopo l’introduzione routinaria della caratterizzazione molecolare nella pratica clinica, sono state analizzate le caratteristiche clinico-patologiche dei tumori dell’endometrio in una casistica real-world. Solo l’istologia sierosa e il grading elevato per il gruppo molecolare p53 abnormal e l’istologia endometrioide, il basso grading e l’invasione linfo-vascolare focale/assente per il gruppo molecolare NSMP si sono dimostrate essere significativamente correlate al fenotipo molecolare, in linea con i dati della letteratura. L’analisi che valutava l’impatto del fenotipo molecolare sullo stadio di malattia non era significativa dal punto di vista statistico. Il limite dello studio è sicuramento rappresentato dal numero limitato di pazienti reclutate, a sua volta dovuto al fatto che solo di recente è stata introdotta la routinaria determinazione molecolare del tumore dell’endometrio. Inoltre, il breve follow up non ha permesso la valutazione real-life dell’impatto prognostico del fenotipo molecolare, per cui in futuro è auspicabile ampliare la casistica e aggiornare il dato con un congruo follow up al fine di avere anche degli esiti di outcome.
Caratteristiche clinico-patologiche associate ai sottogruppi molecolari di tumore dell'endometrio: casistica monocentrica.
BEVILACQUA, ARIANNA
2022/2023
Abstract
In Italy, endometrial cancer ranks third among all female cancers in women aged 50-69 years. The Cancer Genome Atlas Research Network has defined the molecular stratification of endometrial cancer into four different molecular groups: POLE-mutant in 7% of women with this neoplasm, MMRd (mismatch repair deficient) in 28%, p53 abnormal in 26% and NSMP (no specific molecular profile) in 39% of endometrial cancers. From retrospective clinical trials carried out in the past, it has been possible to draw information on the prognosis of these molecular groups and their clinicopathological features. At the moment, this information has not yet been analysed prospectively. The purpose of the present study is to evaluate the clinicopathological features of a cohort of patients with endometrial cancer and known molecular data in order to establish their association in a real-world monocentric study. 70 patients with endometrial cancer and known molecular data were included in the study, who were referred for new diagnosis by the Istituto Oncologico Veneto in Padua and the Clinica Ginecologica of the Hospital – University of Padua in the period 2021-2022. The association between molecular phenotype and clinicopathological features (histology, FIGO stage, grading and lymphovascular invasion) was measured by Pearson’s chi-square test. In addition, a multivariate regression analysis was conducted to assess the impact of molecular phenotype on disease stage at diagnosis. Of the 70 patients examined, 10% (n = 7) belonged to the POLE mutant molecular group, 30% (n = 21) to the MMRd group, 20% (n = 14) to the p53 abnormal group and 39% (n = 27) to the NSMP group. Regarding the association between clinicopathological features and molecular phenotype, few correlations were statistically significant: in particular, in the p53 abnormal group, serous histology and high grading; in the NSMP group, endometrioid histology, low grading and absent/focal lymphovascular invasion. Analysis to assess the impact of molecular phenotype on disease stage was not statistically significant. For the first time after the introduction of molecular characterisation into clinical practice, the clinicopathological features of endometrial carcinomas were analysed in a real-world study. Only serous histology and high grading for the p53 abnormal molecular group and endometrioid histology, low grading and focal/absent lymphovascular invasion for the NSMP group proved to be significantly correlated with the molecular phenotype, consistent with literature data. The analysis assessing the impact of molecular phenotype on disease stage was not statistically significant. The limitation of the study is certainly the limited number of patients recruited, due to the fact that the routine molecular determination of endometrial cancer has recently been introduced. Furthermore, the short follow up did not allow real life evaluation of the prognostic impact of the molecular phenotype, so that in the future it would be desirable to expand the case series and update the data with a congruous follow up.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/47006