Microsatellite instability and sex differences in resectable gastric cancer – A pooled analysis of three European cohorts

Quaas, Alexander; Biesma, Hedde D.; Wagner, Anna Dorothea; Verheij, Marcel; Henegouwen, Mark I. van Berge; Schoemig-Markiefka, Birgid; Pamuk, Aylin; Zander, Thomas; Siemanowski, Janna; Sikorska, Karolina; Egthuijsen, J.M.P.; Kranenbarg, Elma Meershoek-Klein; Velde, Cornelis J.H. van de; Buettner, Reinhard; Alakus, Hakan; Cats, Annemieke; Ylstra, Bauke; Laarhoven, Hanneke W.M. van; Grieken, Nicole C.T. van

doi:10.1016/j.ejca.2022.06.025

Cited by 14 publications

(14 citation statements)

References 37 publications

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“…As shown in our previous study and confirmed by others, this retrospective exploratory analysis confirmed that patients with MSI-H tumors demonstrated significantly increased survival after neoadjuvant CTx (Kohlruss et al 2021;Quaas et al 2022). This superior survival was specifically conspicuous considering the striking good survival of females, but not of men with MSI-H tumors in the group of patients treated without taxane.…”

Section: Discussionsupporting

confidence: 87%

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Microsatellite instability and sex-specific differences of survival in gastric cancer after neoadjuvant chemotherapy without and with taxane: An observational study in real world patients

Hiltner

Kohlruss

Herz

et al. 2023

J Cancer Res Clin Oncol

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Purpose To investigate the prognostic role of microsatellite instability (MSI) in association with sex of patients treated with platinum/fluoropyrimidine neoadjuvant chemotherapy (CTx) with or without a taxane-containing compound. Methods Of the 505 retrospectively analyzed patients with gastric or gastroesophageal adenocarcinoma, 411 patients were treated without taxane and 94 patients with a taxane-containing compound. MSI was determined using standard assays. Results Females demonstrated a better overall survival (OS) than males in the non-taxane group (HR, 0.59; 95% CI 0.41–0.86; p = 0.005), whereas no significant difference was found in the taxane group (HR 1.22; 95% CI 0.55–2.73, p = 0.630). MSI-High (-H) was associated with a better prognosis in both groups (without taxane: HR 0.56; 95% CI 0.33–0.97; p = 0.038; with taxane: HR 0.28; 95% CI 0.04–2.02, p = 0.204). In the non-taxane group, female MSI-H patients showed the best OS (HR 0.18, 95% CI 0.05–0.73; p = 0.016), followed by the female microsatellite stable (MSS) (HR 0.67, 95% CI 0.46–0.98, p = 0.040) and the male MSI-H group (HR 0.76; 95% CI 0.42–1.37, p = 0.760) taken the male MSS group as reference. In the taxane group, female and male MSI-H patients demonstrated the best OS (female MSI-H: HR 0.05, 95% CI 0.00–240.46; male MSI-H: HR 0.45, 95% CI 0.61–3.63, p = 0.438), whereas the female MSS group showed a decreased OS (HR 1.39 95% CI 0.62–3.12, p = 0.420) compared to male MSS patients. Conclusion OS in gastric/gastroesophageal cancer after CTx might depend on sex and MSI status and may differ between patients treated with or without a taxane compound in the chemotherapeutic regimen.

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Section: Discussionsupporting

confidence: 87%

“…In particular, females with MSI-H tumors showed extraordinarily good survival after neoadjuvant CTx compared to males with MSI-H and microsatellite stable (MSS) tumors, and also compared to females with MSS tumors (Kohlruss et al 2021). Similar results were demonstrated in a large meta-analysis including 1307 tumors (Quaas et al 2022).…”

Section: Introductionsupporting

confidence: 64%

Microsatellite instability and sex-specific differences of survival in gastric cancer after neoadjuvant chemotherapy without and with taxane: An observational study in real world patients

Hiltner

Kohlruss

Herz

et al. 2023

J Cancer Res Clin Oncol

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“…In Germany, a similar approach to this study was employed, where a panel of 5 mononucleotide repeats was used to evaluate 452 GC patients, resulting in a prevalence of 7.5% for MSI-H 35 . In 2022, another study conducted in Germany involving a large cohort of 1307 GC patients reported a prevalence of 8.8% 36 . Additionally, a study on German Caucasian patients revealed a prevalence of 7.3% in this particular region 37 .…”

Section: Discussionmentioning

confidence: 99%

Low incidence of microsatellite instability in gastric cancers and its association with the clinicopathological characteristics: a comparative study

Talari,

Bozorg,

Zeinali

et al. 2023

Sci Rep

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Gastric cancer is a complex heterogeneous disease with different molecular subtypes that have clinical implications. It is characterized by high mortality rates and limited effective therapies. Microsatellite instability (MSI) has been recognized as a subgroup with a good prognosis based on TCGA and ACRG categorizations. Besides its prognostic and predictive value, gastric cancers with high MSI exhibit different clinical behaviors. The prevalence of high MSI has been assessed in gastric cancer worldwide, especially in East Asia, but there is a lack of such information in the Middle East. Therefore, this study aimed to investigate the incidence and status of MSI in Iranian gastric cancer patients using 53 samples collected from 2015 to 2020 at Taleghani Hospital Medical Center. DNA from tumoral and normal tissues were extracted and assessed through multiplex-PCR based on five mononucleotide repeats panel. Clinicopathological variables, including age, sex, Lauren classification, lymph node involvement, TNM stage, differentiation, localization, and tumor size, were also analyzed. With 2 males and 2 females, high microsatellite instability represented a small subgroup of almost 7.5% of the samples with a median age of 60.5 years. High microsatellite instability phenotypes were significantly associated with patients aged 68 years and older (p‑value of 0.0015) and lower lymph node involvement (p‑value of 0.0004). Microsatellite instability was also more frequent in females, with distal gastric location, bigger tumor size, and in the intestinal type of gastric cancer rather than the diffuse type.

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“…Dass sich hieraus weitere geschlechtssensible Faktoren mit klinischen Auswirkungen ableiten lassen, zeigten Quaas et al. [ 65 ] in einer hochaktuellen, gepoolten Analyse von drei europäischen Kohorten. Hier zeigten Frauen in der Subgruppe der operablen MSI-high-Magenkarzinome einen signifikanten Überlebensvorteil im Vergleich zu ihrem männlichen Gegenpart.…”

Section: Gastrointestinale Tumorenunclassified

Sex-specific differences of special tumor diseases

Lehnen

Hallek

2023

Innere Medizin

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Zusammenfassung Hintergrund Zahlreiche Daten zeigen, dass Geschlecht und Gender als relevante Modulatoren bestimmter onkologischer und hämatologischer Erkrankungen einen zunehmenden Stellenwert in der Präzisionsmedizin verdient haben. Dieser Beitrag soll eine Zusammenfassung des aktuellen Wissensstands über Geschlechtsunterschiede in Inzidenz und Outcome spezieller Tumorerkrankungen bieten und mögliche zugrunde liegende Ursachen näher beleuchten. Material und Methoden Auswertung und Diskussion von Grundlagenarbeiten, Metaanalysen und klinischen Studien Ergebnisse Es bestehen für eine Vielzahl der onkologischen Erkrankungen signifikante geschlechtsspezifische Unterschiede in Inzidenz, Ansprechraten und Mortalität. Zumeist haben Männer ein schlechteres Outcome, während Frauen höhere therapieassoziierte Toxizität und distinkte Präsentationen in jungem Alter aufweisen. Hormonelle, immunologische und pharmakologische Ursachen liegen nahe. Schlussfolgerung Eine fortschrittliche in Bezug auf die einzelnen Patient*innen individualisierte Therapie in Onkologie und Hämatologie wird sich zukünftig daran messen, die bestehenden relevanten Unterschiede zwischen den Geschlechtern im klinischen Alltag zu berücksichtigen und in Studien zugrunde liegende Mechanismen weiter zu beleuchten, um eine bestmögliche Behandlung für onkologische Patient*innen zu garantieren und zukünftig zu optimieren.

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Microsatellite instability and sex differences in resectable gastric cancer – A pooled analysis of three European cohorts

Cited by 14 publications

References 37 publications

Microsatellite instability and sex-specific differences of survival in gastric cancer after neoadjuvant chemotherapy without and with taxane: An observational study in real world patients

Microsatellite instability and sex-specific differences of survival in gastric cancer after neoadjuvant chemotherapy without and with taxane: An observational study in real world patients

Low incidence of microsatellite instability in gastric cancers and its association with the clinicopathological characteristics: a comparative study

Sex-specific differences of special tumor diseases

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