Pulmonary immunohistochemical markers may be positive in gastric adenocarcinomas associated with autoimmune metaplastic atrophic gastritis

BACKGROUND: Autoimmune metaplastic atrophic gastritis (AMAG) causes pulmonary trans-differentiation of the gastric mucosa and is known to increase the risk of developing gastric adenocarcinoma. AMAG-associated gastric adenocarcinomas were examined for immunoreactivity for TTF-1 and Napsin A. DESIGN: Eighteen AMAG-associated gastric adenocarcinomas and 36 non-AMAG-associated gastric adenocarcinomas were stained for TTF-1 (clones SP141 and 8G7G3/1) and Napsin A (clone 1P64) by immunohistochemistry. AMAG stage and staining patterns were characterized. RESULTS: The AMAG group was older (mean age 74 vs. 65 years) and was not significantly different with regard to sex or tumour differentiation. Zero (0%) AMAG cases were classified as early phase, four (22%) as florid phase and 14 (78%) as end stage. AMAG-associated adenocarcinomas showed more frequent TTF-1 immunoreactivity compared to control adenocarcinomas in both clone SP141 (39% vs. 11%; P = 0.04) and 8G7G3/1 (22% vs. 6%; P = 0.17). AMAG-associated adenocarcinomas showed more frequent Napsin A immunoreactivity compared to control adenocarcinomas (28% vs. 0%; P < 0.01). Immunoreactivity in AMAG-associated adenocarcinomas was patchy, ranging from 1% to 20% of tumour cells staining positive (1+ to 3+ intensity). In the AMAG cases with background gastric mucosa (n = 14), the background showed TTF-1 positive foci in seven (50%) cases (both clones) versus one (3%; clone SP141) to two (6%; clone 8G7G3/1) of 33 controls (P < 0.01) and Napsin A positive foci in five (36%) cases versus zero (0%) controls (P < 0.01). Staining in background mucosa was also patchy, involving 1%-10% of gastric glands without intestinal metaplasia. CONCLUSION: TTF-1 and Napsin A immunoreactivity was present in the background gastric mucosa almost exclusively in the AMAG-associated cases. This immunoreactivity is also present in AMAG-associated adenocarcinomas more commonly than non-AMAG-associated adenocarcinomas. This knowledge may aid pathologists in avoiding the pitfall of diagnosing metastatic lung cancer, as the expression is patchy and may also be seen in atrophic background mucosa.