Can the tumor-agnostic evaluation of MSI/MMR status be the common denominator for the immunotherapy treatment of patients with several solid tumors?

Fanale, Daniele; Corsini, Lidia Rita; Scalia, R.; Brando, Chiara; Cucinella, A.; Madonia, G; Dimino, Alessandra; Filorizzo, Clarissa; Barraco, Nadia; Bono, Marco; Fiorino, Alessia; Magrin, Luigi; Sciacchitano, Roberta; Perez, Alessandro; Russo, Tancredi Didier Bazan; Pantuso, Gianni; Russo, Antonio; Bazan, Viviana

doi:10.1016/j.critrevonc.2022.103597

Cited by 20 publications

(15 citation statements)

References 177 publications

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“…Also, this data could provide helpful suggestions and insights that could contribute to the improvement of the current guidelines, greatly reducing the underdiagnosis of this inherited genetic condition. Consequently, this information could have a strong clinical impact on the choice of the best therapeutic option by clinicians, by allowing the selection of subgroups of CRC patients affected by LS who may benefit from immunotherapy treatments (61). However, it should be noted that our study in addressing the proposed aims shows some limitations, such as small sample size and missing data on MMR status, suggesting that greater information about MMR status of CRCs and a larger study cohort to determine more accurate detection rates for LS are needed.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Impact of Different Selection Approaches for Identifying Lynch Syndrome-Related Colorectal Cancer Patients: Unity Is Strength

et al. 2022

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Lynch syndrome (LS) is an inherited genetic condition associated with increased predisposition to colorectal cancer (CRC) and other tumors and is caused by germline mutations in Mismatch Repair (MMR) or EPCAM genes. The identification of LS carriers is currently based on germline testing of subjects with MMR-deficient (dMMR) tumors or fulfilling clinical criteria, but the most efficient strategies to select patients who should be offered genetic testing are yet not well defined. In order to assess the most suitable selection mode to identify LS-related CRC patients, we retrospectively collected and analyzed all clinical and molecular information of 854 CRC patients, recruited from 2013 to 2021 at the University Hospital Policlinico “P. Giaccone” of Palermo (Italy), 100 of which were selected based on revised Bethesda guidelines, Amsterdam criteria II, or tissue MMR deficiency, and genetically tested for germline variants in LS-susceptibility genes. Our study showed that 32 out of 100 CRC patients harbored germline likely pathogenic/pathogenic variants in MMR genes. The analysis of tissue microsatellite instability (MSI) status according to the revised Bethesda guidelines has been to be the best selection approach. However, using different selection approaches as complementary strategies is useful to identify LS carriers, reducing underdiagnosis of this syndrome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impact of Different Selection Approaches for Identifying Lynch Syndrome-Related Colorectal Cancer Patients: Unity Is Strength

et al. 2022

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“…As far as genetic diseases are concerned, in one study on endometrioid OC which is associated with Lynch syndrome, TILs and peritumoral lymphocytes did not show any relationship with mismatch repair (MMR) status/microsatellite instability (MSI) [ 104 , 105 ]. TILs are elevated in BRCA1 -mutated ovarian carcinomas and have been included in a set of histological criteria predicting BRCA1 mutations in HGSCs, although showing only a high negative predictive value [ 106 ].…”

Section: Tils In Ovarian Cancermentioning

confidence: 99%

Prognostic and Predictive Role of Tumor-Infiltrating Lymphocytes (TILs) in Ovarian Cancer

Fanale

Dimino

Pedone

et al. 2022

Cancers

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In the last decade, tumor-infiltrating lymphocytes (TILs) have been recognized as clinically relevant prognostic markers for improved survival, providing the immunological basis for the development of new therapeutic strategies and showing a significant prognostic and predictive role in several malignancies, including ovarian cancer (OC). In fact, many OCs show TILs whose typology and degree of infiltration have been shown to be strongly correlated with prognosis and survival. The OC histological subtype with the higher presence of TILs is the high-grade serous carcinoma (HGSC) followed by the endometrioid subtype, whereas mucinous and clear cell OCs seem to contain a lower percentage of TILs. The abundant presence of TILs in OC suggests an immunogenic potential for this tumor. Despite the high immunogenic potential, OC has been described as a highly immunosuppressive tumor with a high expression of PD1 by TILs. Although further studies are needed to better define their role in prognostic stratification and the therapeutic implication, intraepithelial TILs represent a relevant prognostic factor to take into account in OC. In this review, we will discuss the promising role of TILs as markers which are able to reflect the anticancer immune response, describing their potential capability to predict prognosis and therapy response in OC.

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“…However, there is a lack of consensus regarding individual gene mutation rates among studies. The relationship between individual gene mutations and mismatch repair (MMR) status and patients’ prognosis also remains controversial [ 11 , 13 , 14 ]. Moreover, there is a lack of comprehensive data on SBA genomic alterations reported from Asia, apart from one study on the genomic profile of Chinese SBA cohorts [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing

et al. 2022

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Background Small bowel adenocarcinomas (SBAs) are rare and there is little comprehensive data on SBA genomic alterations for Asian patients. This study aimed to profile genomic alterations of SBA in Japanese patients using targeted next-generation sequencing (NGS). Methods We examined 22 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by NGS. Mismatch repair (MMR) status was determined by immunohistochemical analysis. Mucin phenotypes were classified as gastric (G), intestinal (I), gastrointestinal (GI), and null (N) types on MUC2, MUC5AC, MUC6, and CD10 immunostaining. Results The most common genomic alterations found in SBA tumors were TP53 (n = 16), followed by KRAS (n = 6), APC (n = 5), PIK3CA (n = 4), CTNNB1 (n = 3), KIT (n = 2), BRAF (n = 2), CDKN2A (n = 2), and PTEN (n = 2). Deficient MMR tumors were observed in 6 out of 22 patients. Tumor mucin phenotypes included 2 in G-type, 12 in I-type, 3 in GI-type, and 5 in N-type. APC and CTNNB1 mutations were not found in G-type and GI-type tumors. KRAS mutations were found in all tumor types except for G-type tumors. TP53 mutations were found in all tumor types. Although no single gene mutation was associated with overall survival (OS), we found that KRAS mutations were associated with significant worse OS in patients with proficient MMR tumors. Conclusions SBA genomic alterations in Japanese patients do not differ significantly from those reports in Western countries. Tumor localization, mucin phenotype, and MMR status all appear to impact SBA gene mutations.

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Can the tumor-agnostic evaluation of MSI/MMR status be the common denominator for the immunotherapy treatment of patients with several solid tumors?

Cited by 20 publications

References 177 publications

Impact of Different Selection Approaches for Identifying Lynch Syndrome-Related Colorectal Cancer Patients: Unity Is Strength

Impact of Different Selection Approaches for Identifying Lynch Syndrome-Related Colorectal Cancer Patients: Unity Is Strength

Prognostic and Predictive Role of Tumor-Infiltrating Lymphocytes (TILs) in Ovarian Cancer

Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing

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