MMR deficiency is frequent in colorectal carcinomas with diffuse SLFN11 immunostaining: clinicopathologic and molecular study of 31 cases identified among 3,300 tumors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00669806%3A_____%2F25%3A10496353" target="_blank" >RIV/00669806:_____/25:10496353 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11140/25:10496353

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1ITJ-1Y~k0" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1ITJ-1Y~k0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/2056-4538.70025" target="_blank" >10.1002/2056-4538.70025</a>

Jazyk výsledku

angličtina

Název v původním jazyce

MMR deficiency is frequent in colorectal carcinomas with diffuse SLFN11 immunostaining: clinicopathologic and molecular study of 31 cases identified among 3,300 tumors

Popis výsledku v původním jazyce

Schlafen 11 (SLFN11), a regulator of cell fate following DNA injury, sensitizes tumor cells to DNA-damaging agents. Patients with SLFN11-positive tumors may benefit from DNA-damaging chemotherapies. SLFN11 has been studied in different types of cancer including colorectal carcinomas. However, colorectal carcinomas with diffuse positivity (expression in &gt;=80% of tumor cells) have not been meticulously characterized. SLFN11 immunostaining of tumor microarrays (TMAs) with 3,300 primary CRCs identified 65 (~2.0%) tumors with focal staining (&lt;10% of tumor nuclei positive), 83 (~2.5%) with patchy (&gt;=10% and &lt;80%) and 51 (~1.5%) with diffuse (&gt;=80%) SLFN11 positivity. The latter was confirmed on full sections from donor blocks in 31 (~1%) cases, which were further studied including evaluation of additional immunohistochemical markers, genotyping with targeted DNA sequencing, and assessment of microsatellite instability. SLFN11-positive carcinomas were mostly (21/31, 68%) right-sided tumors with a female predominance (21/31, 68%) and median age of 67 years. Eighteen of 31 (58%) contained areas of mucinous differentiation. Deficiency of mismatch repair proteins was detected in 65% (20/31) of SLFN11-positive carcinomas. Moreover, MLH1 (n = 2), MSH2, MSH6, and PMS2 germline mutations were identified in 25% (5/20) of patients with mismatch repair deficient tumors. BRAF p.V600E mutation was found in 45% (9/20) of mismatch repair deficient, but only 1 of 11 proficient tumors. Colorectal carcinomas with diffuse SLFN11 positivity were often mismatch repair deficient tumors with their typical clinical, morphological, and molecular characteristics.

Název v anglickém jazyce

MMR deficiency is frequent in colorectal carcinomas with diffuse SLFN11 immunostaining: clinicopathologic and molecular study of 31 cases identified among 3,300 tumors

Popis výsledku anglicky

Schlafen 11 (SLFN11), a regulator of cell fate following DNA injury, sensitizes tumor cells to DNA-damaging agents. Patients with SLFN11-positive tumors may benefit from DNA-damaging chemotherapies. SLFN11 has been studied in different types of cancer including colorectal carcinomas. However, colorectal carcinomas with diffuse positivity (expression in &gt;=80% of tumor cells) have not been meticulously characterized. SLFN11 immunostaining of tumor microarrays (TMAs) with 3,300 primary CRCs identified 65 (~2.0%) tumors with focal staining (&lt;10% of tumor nuclei positive), 83 (~2.5%) with patchy (&gt;=10% and &lt;80%) and 51 (~1.5%) with diffuse (&gt;=80%) SLFN11 positivity. The latter was confirmed on full sections from donor blocks in 31 (~1%) cases, which were further studied including evaluation of additional immunohistochemical markers, genotyping with targeted DNA sequencing, and assessment of microsatellite instability. SLFN11-positive carcinomas were mostly (21/31, 68%) right-sided tumors with a female predominance (21/31, 68%) and median age of 67 years. Eighteen of 31 (58%) contained areas of mucinous differentiation. Deficiency of mismatch repair proteins was detected in 65% (20/31) of SLFN11-positive carcinomas. Moreover, MLH1 (n = 2), MSH2, MSH6, and PMS2 germline mutations were identified in 25% (5/20) of patients with mismatch repair deficient tumors. BRAF p.V600E mutation was found in 45% (9/20) of mismatch repair deficient, but only 1 of 11 proficient tumors. Colorectal carcinomas with diffuse SLFN11 positivity were often mismatch repair deficient tumors with their typical clinical, morphological, and molecular characteristics.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

The Journal of Pathology

ISSN

0022-3417

e-ISSN

1096-9896

Svazek periodika

11

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

e70025

Kód UT WoS článku

001449341500001

EID výsledku v databázi Scopus

2-s2.0-105000698928