Universal screening for mismatch repair deficiency in gastrointestinal cancers in a reference center in Mexico.
Authors: Hernandez-Felix Jorge Humberto , Meneses-Medina Monica Isabel , Domínguez Armando Gamboa , Rosas Camargo Vanessa , Jiménez Meza Marco Antonio , Galindo-Garcia Tania Alejandra , Candanedo-Gonzalez Fernando , rios Valencia Javier , Alcocer Carmona Andrea , Ogarrio Cano Laura , Rodriguez Camacho Heidi Dalay , Escorza Salvador , Huitzil Melendez Fidel David David 
Published: January 2025

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Background:
Gastrointestinal (GI) cancers have a poor prognosis. With the availability of immunotherapy for tumors with deficient mismatch repair (dMMR), identifying these patients has become increasingly important. Universal dMMR screening across all GI cancers is uncommon, and its prevalence has not been well studied prospectively. In Mexico, the prevalence of dMMR is unknown, even though GI cancers account for a large portion of new cancer cases and cancer-related deaths. Our objective was to prospectively determine the prevalence of dMMR in GI cancers at a referral center in Mexico.
Methods:
Prospective universal screening for dMMR began in March 2024. Primary tumor sites included were esophagus, stomach, pancreas, biliary tract, small intestine, colon, and rectum. Histologies included were adenocarcinoma, squamous cell, or mixed. All consecutive patients were included regardless of age, clinical stage or medical history. MMR status was determined by immunohistochemistry, analyzing expression of MLH1, PMS2, MSH2, and MSH6. This abstract presents the results from the first six months of this universal screening.
Results:
A total of 161 GI cancers were included (see Table). Prevalence of dMMR was 9.3% (n=15). The highest prevalence was in gastric cancer (13.3%, 2/15), followed by colon (12.1%, 7/58), pancreatic (11.1%, 4/36), and bile duct (8.3%, 2/24) cancer. MMR status was not performed in 9.3% (n=15) of cases. Combined deficiency was found in 60% (9/15) for MLH1/PMS2 and 20% (3/15) for MSH2/MSH6. Isolated deficiency occurred in 20% (3/15) for PMS2 and 13.3% (2/15) for MSH2. No difference in age or clinical stage was observed between MMR status groups.
Conclusions:
The high prevalence of dMMR, along with the poor prognosis and availability of immunotherapy based treatments, supports the need for universal screening. The high prevalence of dMMR in pancreatobiliary cancers was notable. Implementation efforts in our institution are essential to obtain MMR status in all cases.

Characteristics of population.

pMMRn=131 (%)
dMMRn=15 (%)
Not performedn=15 (%)
Totaln=161
p value

Gender
Male
63 (48.1)
10 (66.7)
7 (46.7)
80 (49.7)
0.38

Female
68 (51.9)
5 (33.3)
8 (53.3)
81 (50.3)

Age
Median (IQR)
65 (54 -72)
52 (43 -80)
65 (57 -71)
65 (53 -72)
0.52

Histology
Adenocarcinoma
130 (99.2)
15 (100.0)
14 (93.3)
159 (98.8)
N/A

Mixed
1 (0.8)
0 (0.0)
0 (0.0)
1 (0.6)

Squamous Cell
0 (0.0)
0 (0.0)
1 (6.7)
1 (0.6)

Clinical Stage
Unknown
12 (9.2)
1 (6.7)
1 (6.7)
14 (8.7)
0.49

Localized
24 (18.3)
2 (13.3)
2 (13.3)
28 (17.4)

Locally advanced
40 (30.5)
8 (53.3)
3 (20.0)
51 (31.7)

Metastatic
55 (42.0)
4 (26.7)
9 (60.0)
68 (42.2)

Tumor site
Esophageal
9 (6.9)
0 (0.0)
1 (6.7)
10 (6.2)
N/A

Gastric
13 (9.9)
2 (13.3)
0 (0.0)
15 (9.3)

Small B.
1 (0.8)
0 (0.0)
0 (0.0)
1 (0.6)

Bile duct
14 (10.7)
2 (13.3)
8 (53.3)
24 (14.9)

Pancreas
29 (22.1)
4 (26.7)
3 (20.0)
36 (22.4)

Colon
50 (38.2)
7 (46.7)
1 (6.7)
58 (36.0)

Rectal
15 (11.5)
0 (0.0)
2 (13.3)
17 (10.6)