A Novel Approach to Preoperative Risk Stratification in Endometrial Cancer: The Added Value of Immunohistochemical Markers

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F19%3A00070848" target="_blank" >RIV/65269705:_____/19:00070848 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/19:00110914

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fonc.2019.00265/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fonc.2019.00265/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fonc.2019.00265" target="_blank" >10.3389/fonc.2019.00265</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A Novel Approach to Preoperative Risk Stratification in Endometrial Cancer: The Added Value of Immunohistochemical Markers

Popis výsledku v původním jazyce

Background: The current model used to preoperatively stratify endometrial cancer (EC) patients into low-and high-risk groups is based on histotype, grade, and imaging method and is not optimal. Our study aims to prove whether a new model incorporating immunohistochemical markers, L1CAM, ER, PR, p53, obtained from preoperative biopsy could help refine stratification and thus the choice of adequate surgical extent and appropriate adjuvant treatment. Materials and Methods: The following data were prospectively collected from patients operated for EC from January 2016 through August 2018: age, pre- and post-operative histology, grade, lymphovascular space invasion, L1CAM, ER, PR, p53, imaging parameters obtained from ultrasound, CT chest/abdomen, final FIGO stage, and current decision model (based on histology, grade, imaging method). Results: In total, 132 patients were enrolled. The current model revealed 48% sensitivity and 89% specificity for high-risk group determination. In myometrial invasion &gt;50%, lower levels of ER (p = 0.024), PR (0.048), and higher levels of L1CAM (p = 0.001) were observed; in cervical involvement a higher expression of L1CAM (p = 0.001), lower PR (p = 0.014); in tumors with positive LVSI, higher L1CAM (p = 0.014); in cases with positive LN, lower expression of ER/PR (p &lt; 0.001), higher L1CAM (p = 0.002) and frequent mutation of p53 (p = 0.008). Cut-offs for determination of high-risk tumors were established: ER &lt;78% (p = 0.001), PR &lt;88% (p = 0.008), and L1CAM &gt;= 4% (p &lt; 0.001). The positive predictive values (PPV) for ER, PR, and L1CAM were 87% (60.8-96.5%), 63% (52.1-72.8%), 83% (70.5-90.8%); the negative predictive values (NPV) for each marker were as follows: 59% (54.5-63.4%), 65%(55.6-74.0%), and 77%(67.3-84.2%). Mutation of p53 revealed PPV 94% (67.4-99.1%) and NPV 61% (56.1-66.3%). When immunohistochemical markers were included into the current diagnostic model, sensitivity improved (48.4 vs. 75.8%, p &lt; 0.001). PPV was similar for both methods, while NPV (i.e., the probability of extremely low risk in negative test cases) was improved (66 vs. 78.9%, p &lt; 0.001). Conclusion: We proved superiority of new proposed model using immunohistochemical markers over standard clinical practice and that new proposed model increases accuracy of prognosis prediction. We propose wider implementation and validation of the proposed model.

Název v anglickém jazyce

A Novel Approach to Preoperative Risk Stratification in Endometrial Cancer: The Added Value of Immunohistochemical Markers

Popis výsledku anglicky

Background: The current model used to preoperatively stratify endometrial cancer (EC) patients into low-and high-risk groups is based on histotype, grade, and imaging method and is not optimal. Our study aims to prove whether a new model incorporating immunohistochemical markers, L1CAM, ER, PR, p53, obtained from preoperative biopsy could help refine stratification and thus the choice of adequate surgical extent and appropriate adjuvant treatment. Materials and Methods: The following data were prospectively collected from patients operated for EC from January 2016 through August 2018: age, pre- and post-operative histology, grade, lymphovascular space invasion, L1CAM, ER, PR, p53, imaging parameters obtained from ultrasound, CT chest/abdomen, final FIGO stage, and current decision model (based on histology, grade, imaging method). Results: In total, 132 patients were enrolled. The current model revealed 48% sensitivity and 89% specificity for high-risk group determination. In myometrial invasion &gt;50%, lower levels of ER (p = 0.024), PR (0.048), and higher levels of L1CAM (p = 0.001) were observed; in cervical involvement a higher expression of L1CAM (p = 0.001), lower PR (p = 0.014); in tumors with positive LVSI, higher L1CAM (p = 0.014); in cases with positive LN, lower expression of ER/PR (p &lt; 0.001), higher L1CAM (p = 0.002) and frequent mutation of p53 (p = 0.008). Cut-offs for determination of high-risk tumors were established: ER &lt;78% (p = 0.001), PR &lt;88% (p = 0.008), and L1CAM &gt;= 4% (p &lt; 0.001). The positive predictive values (PPV) for ER, PR, and L1CAM were 87% (60.8-96.5%), 63% (52.1-72.8%), 83% (70.5-90.8%); the negative predictive values (NPV) for each marker were as follows: 59% (54.5-63.4%), 65%(55.6-74.0%), and 77%(67.3-84.2%). Mutation of p53 revealed PPV 94% (67.4-99.1%) and NPV 61% (56.1-66.3%). When immunohistochemical markers were included into the current diagnostic model, sensitivity improved (48.4 vs. 75.8%, p &lt; 0.001). PPV was similar for both methods, while NPV (i.e., the probability of extremely low risk in negative test cases) was improved (66 vs. 78.9%, p &lt; 0.001). Conclusion: We proved superiority of new proposed model using immunohistochemical markers over standard clinical practice and that new proposed model increases accuracy of prognosis prediction. We propose wider implementation and validation of the proposed model.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Oncology

ISSN

2234-943X

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

APR 12

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

13

Strana od-do

265

Kód UT WoS článku

000464373800001

EID výsledku v databázi Scopus

2-s2.0-85067459380