Gastric Carcinomas With Lymphoid Stroma: An Evaluation of the Histopathologic and Molecular Features.

Gastric carcinoma with lymphoid stroma is an uncommon variant enriched for mutually exclusive Epstein-Barr virus (EBV) positivity and mismatch repair (MMR) deficiency. We performed this study to evaluate molecular alterations in this morphologically homogeneous subtype and compare them with 295 conventional gastric cancers analyzed in The Cancer Genome Atlas study. We identified 31 study cases and subjected them to in situ hybridization for EBV-encoded RNAs and assessment for MMR status. Immunostains for PD-L1, ß-catenin, and HER2 were performed; extracted DNA was sequenced with a Comprehensive Cancer Panel. Most study patients were older adult men with stage I or II disease (76%). Tumors were classified as EBV/MMR-proficient (MMR-P) (n=7), EBV/MMR deficient (n=12), and EBV/MMR-P (n=12). EBV/MMR-P tumors were usually located in the proximal stomach (83%) and showed heterogenous growth patterns with glandular differentiation (83%). Tumors in all groups showed numerous tumor infiltrating lymphocytes and PD-L1 expression, infrequent nuclear ß-catenin accumulation (10%), and lacked both membranous HER2 staining and HER2 amplification. EBV/MMR-deficient tumors showed significantly higher tumor mutation burden (P=0.001) and KRAS alterations (56%) compared with EBV/MMR-P tumors (9%, P=0.05). TP53 variants were more common among EBV/MMR-P tumors (82%) compared with EBV/MMR proficient (0%, P=0.01) and EBV/MMR-deficient (11%, P<0.01) tumors. Alterations in KRAS, ARID1A, PIK3CA, and TP53 followed similar patterns of distribution compared with The Cancer Genome Atlas dataset. We conclude that gastric carcinomas with lymphoid stroma show a spectrum of molecular changes and frequent PD-L1 expression, raising the possibility that this subgroup of tumors may be susceptible to checkpoint inhibitors and/or agents that target receptor tyrosine kinase-mediated signaling.

Squamous-cell carcinoma of the rectum: a rare but curable tumor.

PURPOSE: This study was designed to evaluate one institution's experience with treatment outcomes for rectal squamous-cell carcinoma. METHODS: Using our prospective Colorectal Database, we identified patients diagnosed with rectal squamous-cell carcinoma at our institution between 1983 and 2005. Pathology was rereviewed, tumor immunophenotype was compared to control cases of anal squamous-cell carcinoma and rectal adenocarcinoma, treatment modalities and outcomes were analyzed. RESULTS: Twelve patients were identified (10 females median age, 58 years). Median distal extent of tumors was 7 (range, 5-8) cm from the anal verge. Treatment included chemotherapy only (n = 1), chemoradiation only (n = 2), induction chemotherapy followed by chemoradiation and surgery (n = 2), chemoradiation followed by surgery (n = 5), and surgery followed by chemoradiation (n = 2). The chemotherapy regimen was 5-fluorouracil-based. Radiotherapy total dose was 50.4 Gy (1.8 Gy/day, daily x 5) external iliac and inguinal nodes were not included in the radiation field. Complete clinical responders to chemoradiation (n = 2) received no further treatment. All seven partial responders underwent surgery; six had complete pathologic response; nodal status in two of six was unknown because they had local excision. Immunophenotypical analysis showed similar keratin expression profile between rectal squamous-cell carcinoma (n = 5) and rectal adenocarcinoma (n = 5), which is different from anal squamous-cell carcinoma (n = 10). All patients were alive without evidence of disease at follow-up (median follow-up, 2.6 (range, 0.5-16) years). CONCLUSIONS: Our data suggest that most patients treated with upfront chemoradiation therapy followed by surgery did well. Sphincter-preserving surgery is usually feasible. Clinical judgment of tumor response after chemoradiation is not completely reliable. Immunohistochemistry suggests a common cellular origin for rectal squamous-cell carcinoma and rectal adenocarcinoma, which is different from anal squamous-cell carcinoma.

Sequential preoperative fluorodeoxyglucose-positron emission tomography assessment of response to preoperative chemoradiation: a means for determining longterm outcomes of rectal cancer.

BACKGROUND: We have previously demonstrated that fluorodeoxyglucose-positron emission tomography (FDG-PET) can assess extent of pathologic response of primary rectal cancer to preoperative chemoradiation. Our goal was to determine the prognostic significance of FDG-PET assessment of rectal cancer response to preoperative chemoradiation. STUDY DESIGN: Fifteen patients with locally advanced primary rectal cancer (clinically bulky or tethered, or ultrasound evidence of T3-4 disease, N1 disease, or both) deemed eligible for preoperative radiation and 5-FU-based chemotherapy (5,040 cGy to the pelvis and 2 cycles of bolus 5-FU/leucovorin) were prospectively enrolled from May 1997 to September 1998. FDG-PET was performed before and 4 to 5 weeks after completion of preoperative chemoradiation. FDG-PET parameters included maximum standard uptake value (SUV(max)), total lesion glycolysis (TLG), and visual response score. Patients were prospectively followed after operation, and disease status was determined. RESULTS: All patients demonstrated some degree of response to preoperative therapy based on pathologic examination. At a median followup of 42 months (range 23 to 54 months), 11 patients had no evidence of disease and 4 had died of disease. The mean percentage decrease in SUV(max) (DeltaSUV(max)) was 69% for patients free from recurrence and 37% for patients with recurrence (p = 0.004). DeltaSUV(max) >or= 62.5 and deltaTLG >or= 69.5 were the best predictors of no-evidence-of-disease status and freedom from recurrence. Patients with DeltaSUV(max) >or= 62.5 and deltaTLG >or= 69.5 had significantly improved disease-specific and recurrence-free survival (p = 0.08, 0.02 and p = 0.03, 0.01, respectively). CONCLUSIONS: Our results indicate that FDG-PET assessment of locally-advanced rectal cancer response to preoperative chemoradiation may predict longterm outcomes.