Acellular mucin in lymph nodes isolated from treatment-naïve colorectal cancer resections: a clinicopathologic analysis of 16 cases.

Lymph nodes with acellular mucin harvested from treated colorectal cancers (CRC) are staged as pN0. However, there is variability among pathologists while reporting the pN stage when acellular mucin is found within nodes of untreated CRCs. While the UICC guidelines suggest staging them as pN1, the AJCC and CAP do not offer any recommendations. In order to characterize their clinicopathologic features and outcome, we compared 16 untreated CRCs (study group; mean age: 68 years) harboring nodes with acellular mucin with 34 pN0 and 25 pN1 untreated CRC controls. All tumors were unifocal; 12 (75%) were right-sided lesions. Most cases (75%) showed one node with acellular mucin (range: 1-3). MMR-deficient tumors were significantly more common in the study group (83%) compared to pN0 (33%; p = 0.006) and pN1 controls (8%; p < 0.001). The overall survival of study group patients was closer to pN0 compared to pN1 controls; however, this difference was not statistically significant. In conclusion, untreated CRC that harbor acellular mucin within lymph nodes commonly present as right-sided, MMR-deficient tumors in older women that show a non-mucinous phenotype. While the limited number of cases precludes us from making any formal recommendations about staging, we suggest that the finding of acellular mucin in a node should prompt evaluation of deeper levels (with or without cytokeratin immunohistochemistry) and submission of all pericolonic fat for additional lymph node harvest. Whether acellular mucin in nodes of untreated CRCs is related to the indolent biology of the disease, a robust local immune response or MMR deficiency requires further investigation.

Serum amyloid A immunohistochemical staining patterns in hepatitis.

AIMS: Serum amyloid A is an acute phase reactant that is produced by hepatocytes in response to either inflammatory or neoplastic conditions. Because inflammatory adenomas produce this protein, serum amyloid A immunohistochemistry has been used in the evaluation of hepatocellular neoplasms. However, studies evaluating the expression of this protein in hepatitis are lacking. The aim of this study was to perform serum amyloid A immunostains on medical liver biopsy specimens of patients with common chronic liver diseases and correlate them with disease activity and stage. METHODS AND RESULTS: We performed serum amyloid A immunostains on 160 medical liver biopsies, including 100 cases of hepatitis C virus infection at different stages (20 cases of each) and 20 cases each of hepatitis B viral infection, steatohepatitis and autoimmune hepatitis. The extent and location of staining was recorded and correlated with grade, stage and laboratory values (transaminases, bilirubin and viral load). Data were analysed using the Cochran-Mantel-Haenszel χ2 test for trend. Serum amyloid A staining was present in 130 (81%) cases and was limited to zone 3 perivenular hepatocytes in 66 (41%). Biopsy specimens with less fibrosis and/or mild portal inflammation showed significantly more staining than those with cirrhosis (P < 0.001), or at least moderate inflammatory activity (P < 0.001). There was no significant association between lobular inflammation (P = 0.06), bilirubin levels or viral load and immunohistochemical staining for serum amyloid A. CONCLUSIONS: Our results show that liver biopsy specimens with mildly active chronic hepatitis, early fibrosis and normal serum transaminases show more serum amyloid A immunopositivity compared with cases with more inflammatory activity, fibrosis or transaminitis. These findings indicate that serum amyloid A is expressed primarily in the early phases of disease and might influence progression and/or response to treatment.

Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions.

Expression of cancer/testis (CT) antigens in squamous cell carcinoma of the head and neck: evaluation as markers of squamous dysplasia.

Cancer/testis (CT) antigens, normally only expressed in germ cells of adult testis, can be activated in malignancy as tumor-specific antigens. The potential value of CT antigens as biomarkers in the evaluation of mucosal squamous precursor lesions of the head and neck has not been investigated. The expression of 8 CT antigens (MAGE-A, GAGE, NY-ESO-1, CT7, CT10, SAGE1, CT45 and NXF2) in 76 cases of invasive head and neck squamous cell carcinoma (SCC) was evaluated immunohistochemically. 65 mucosal biopsies of squamous dysplasia and 55 squamous papillomas with dysplasia were analyzed for 6 CT antigens, using an antibody cocktail. Of invasive SCC, 66% (50/76) expressed at least one CT antigen, most commonly MAGE-A (47%). Among the biopsies, only 1 of 55 squamous papillomas was CT-positive, whereas 8 of 65 (12%) squamous dysplasia lesions were CT-positive. These 8 CT-positive biopsies were from 6 patients, 3 of which had concurrent or subsequent SCC. CT antigens are frequently expressed in head and neck SCC; however, there was no difference in the clinicopathological characteristics or behavior of CT-positive tumors compared to CT-negative tumors. The usefulness of CT antigens as positive predictors for SCC in squamous dysplasia biopsies remains to be determined by long-term follow-up in larger cohorts.