Claudin-18.

CONTEXT.­: Claudin-18 is expressed in some gastric cancers. Clinical trials are evaluating it as a therapeutic target. OBJECTIVES.­: To evaluate claudin-18 expression in intestinal metaplasia, dysplasia, and adenocarcinoma of the distal esophagus/gastroesophageal junction and stomach and to evaluate claudin-18 expression in gastric and nongastric neuroendocrine tumors as a marker of gastric origin. DESIGN.­: Samples included gastroesophageal junction with intestinal metaplasia (n = 40), dysplasia (n = 54), and adenocarcinoma (n = 20) and stomach with intestinal metaplasia (n = 79), dysplasia (n = 43), and adenocarcinoma (n = 25). Additionally, gastric (n = 40) and nongastric (n = 322) neuroendocrine tumors were included. Claudin-18 expression was evaluated for any staining as positive and by meeting clinical trial inclusion criteria (≥2+ intensity in ≥50% of tumor). RESULTS.­: Claudin-18 staining was not significantly different across dysplasia categories in the gastroesophageal junction (P = .11) or stomach (P = .12). The rate of positive staining was higher in gastroesophageal junction than stomach for intestinal metaplasia (37 of 40 [92.5%] versus 37 of 79 [46.8%]; P < .001) and high-grade dysplasia (33 of 38 [86.8%] versus 9 of 16 [56.3%]; P = .03). Intestinal metaplasia showed staining in 7 of 37 autoimmune gastritis samples (18.9%) compared with 30 of 42 samples without autoimmune gastritis (71.4%) (P < .001). Adenocarcinoma showed similar staining in gastroesophageal junction (15 of 20; 75.0%) and stomach (17 of 25; 68.0%) (P = .85). Eighty percent (32 of 40) of gastric neuroendocrine tumors were positive for claudin-18 expression, with 57.5% (23 of 40) meeting clinical trial inclusion criteria. Comparatively, 0.62% (2 of 322) of nongastric neuroendocrine tumors showed staining (P < .001). CONCLUSIONS.­: Claudin-18 staining was similar in intestinal metaplasia, dysplasia, and adenocarcinoma. Claudin-18 was negative in most cases of intestinal metaplasia in autoimmune gastritis, indicating that intestinal metaplasia in this setting may differ from other forms. Claudin-18 was sensitive and specific for gastric origin in neuroendocrine tumors.

Diagnostic utility of dual 5-hydroxymethylcytosine/Melan-A immunohistochemistry in differentiating nodal nevus from metastatic melanoma: An effective first-line test for the workup of sentinel lymph node specimen.

BACKGROUND: Distinguishing benign nodal nevus from metastatic melanoma can be diagnostically challenging, with important clinical consequences. Recently, the loss of epigenetic marker, 5-hydroxymethylcytosine (5-hmC) expression by immunohistochemistry has been found in melanomas and atypical melanocytic neoplasms. METHODS: About 41 metastatic melanomas and 20 nodal nevi were retrieved. Nuclear 5-hmC (brown) and cytoplasmic Melan-A Red (red) double immunohistochemical staining was performed. RESULTS: Total or partial loss of nuclear expression of 5-hmC was noted in 40/41 metastatic melanomas; these tumor cells were strongly positive for Melan-A Red, except in one case of desmoplastic melanoma. All cases of nodal nevus showed uniformly retained nuclear expression of 5-hmC accompanied by strong Melan-A Red cytoplasmic staining. In two cases containing both nodal nevus and metastatic melanoma, all tumor cells were positive for Melan-A Red, but a nuclear expression of 5-hmC was selectively absent only in the melanoma tumor cells. CONCLUSION: Dual 5-hmC/Melan-A Red immunohistochemistry is highly specific in distinguishing nodal nevus from metastatic melanoma. Our protocol for brown and red chromogens used in this study provides excellent color contrast and is easy to interpret. Furthermore, this dual staining method allows the preservation of limited tumor tissue, which could be used for potential molecular studies.