Immunophenotypic evaluation of DNA mismatch repair markers in 2 cases of synchronous histomorphologically distinct gastric adenocarcinomas with gastrointestinal stromal tumors of the proximal small bowel.
OBJECTIVE
To assess the prognostic value of combined mismatch DNA repair (MMR) phenotyping in 2 synchronous histomorphologically distinct gastric adenocarcinomas (GADCs), each accompanied by gastrointestinal stromal tumors (GISTs) of the proximal small bowel.


BACKGROUND
A 72-year-old female and a 55-year-old male patient were submitted to partial and total gastrectomy, respectively, with synchronous resection of a GIST in the proximal small bowel. The 2 patients attained contrasting survival outcomes. The female survives disease-free 20 months after surgery having received no chemotherapy. The male who received adjuvant chemotherapy developed metastases in liver and lung, and died 18 months after surgery.


METHODS
We phenotype MSH2 and MLH1 protein expression in tumor relative to matched normal tissue by immunohistochemistry.


RESULTS
Immunohistochemistry analysis revealed different combined MMR phenotypes for the 2 histomorhologically distinct GADCs and similar for both GISTs studied.


CONCLUSIONS
Good and bad prognosis for disease-free survival of patients based on reduced and elevated combined MMR phenotypic expression of the 2 histomorphologically distinct GADCs, could be explained by disease-associated emergence of genomic MMR alterations in the tumor. The impact of synchronous GISTs with common intermediate MMR phenotypes on patient survival is rather incidental and secondary to predominating GADCs.
Athanassiou
Evangelos
E
Department of Surgery, University of Thessalia Medical School, Larissa, Greece. evangelosathanassiou@yahoo.com
Vamvakopoulou
Dimitra N
DN
Zacharoulis
Dimitrios
D
Paroutoglou
George
G
Sioutopoulou
Despina
D
Tepetes
Konstantinos
K
Nomikos
Iakovos
I
Vamvakopoulos
Nicholas C
NC
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000556:secondary* / Q000628:therapy; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D053843:DNA Mismatch Repair; D017809:Fatal Outcome; D005260:Female; D005743:Gastrectomy; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000556:secondary / Q000628:therapy; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000556:secondary / Q000628:therapy; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D021381:Protein Transport; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein