Till S. Clauditz

Expression of Trefoil Factor 1 (TFF1) in Cancer: A Tissue Microarray Study Involving 18,878 Tumors

Background/Objectives: Trefoil factor 1 (TFF1) plays a role in the mucus barrier. Methods: To evaluate the prevalence of TFF1 expression in cancer, a tissue microarray containing 18,878 samples from 149 tumor types and 608 samples of 76 normal tissue types was analyzed through immunohistochemistry (IHC). Results: TFF1 staining was detectable in 65 of 149 tumor categories. The highest rates of TFF1 positivity were found in mucinous ovarian carcinomas (76.2%), colorectal adenomas and adenocarcinomas (47.1–75%), breast neoplasms (up to 72.9%), bilio-pancreatic adenocarcinomas (42.1–62.5%), gastro-esophageal adenocarcinomas (40.4–50.0%), neuroendocrine neoplasms (up to 45.5%), cervical adenocarcinomas (39.1%), and urothelial neoplasms (up to 24.3%). High TFF1 expression was related to a low grade of malignancy in non-invasive urothelial carcinomas of the bladder (p = 0.0225), low grade of malignancy (p = 0.0003), estrogen and progesterone receptor expression (p < 0.0001), non-triple negativity (p = 0.0005) in invasive breast cancer of no special type, and right-sided tumor location (p = 0.0021) in colorectal adenocarcinomas. Conclusions: TFF1 IHC has only limited utility for the discrimination of different tumor entities given its expression in many tumor entities. The link between TFF1 expression and parameters of malignancy argues for a relevant biological role of TFF1 in cancer. TFF1 may represent a suitable therapeutic target due to its expression in only a few normal cell types.

Frequency of Androgen Receptor Positivity in Tumors: A Study Evaluating More Than 18,000 Tumors

Androgen receptor (AR) is a transcription factor expressed in various normal tissues and is a therapeutic target for prostate and possibly other cancers. A TMA containing 18,234 samples from 141 different tumor types/subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. AR positivity was found in 116 tumor types including 66 tumor types (46.8%) with ≥1 strongly positive tumor. Moderate/strong AR positivity was detected in testicular sex cord-stromal tumors (93.3–100%) and neoplasms of the prostate (79.3–98.7%), breast (25.0–75.5%), other gynecological tumors (0.9–100%), kidney (5.0–44.1%), and urinary bladder (5.4–24.2%). Low AR staining was associated with advanced tumor stage (pTa versus pT2-4; p < 0.0001) in urothelial carcinoma; advanced pT (p < 0.0001), high tumor grade (p < 0.0001), nodal metastasis (p < 0.0001), and reduced survival (p = 0.0024) in invasive breast carcinoma; high pT (p < 0.0001) and grade (p < 0.0001) in clear cell renal cell carcinoma (RCC); and high pT (p = 0.0055) as well as high grade (p < 0.05) in papillary RCC. AR staining was unrelated to histopathological/clinical features in 157 endometrial carcinomas and in 221 ovarian carcinomas. Our data suggest a limited role of AR immunohistochemistry for tumor distinction and a prognostic role in breast and clear cell RCC and highlight tumor entities that might benefit from AR-targeted therapy.

MUC5AC expression is linked to mucinous/endometroid subtype, absence of nodal metastasis and mismatch repair deficiency in ovarian cancer

Mucin 5AC (MUC5AC) is a secreted gel-forming mucin which is expressed by mucus producing cells of several organs but can also be found in cancer cells of the ovary, pancreas, and gastrointestinal tract. This study aimed to characterize the expression of MUC5AC and its potential prognostic implications in different ovarian cancer subtypes. MUC5AC expression was analyzed by immunohistochemistry on a tissue microarray containing 603 ovarian cancers. MUC5AC was commonly expressed in mucinous (27/36; 75%) and endometrioid (12/39; 31%) carcinomas, whereas malignant mixed Mullerian tumors (2/27; 7%), high-grade serous (20/373; 5%) and clear cell carcinomas (1/28; 4%) were only rarely MUC5AC positive and also showed lower expression levels. MUC5AC positive endometroid carcinomas and high-grade serous carcinomas lacked lymph node metastases (p = 0.0495 and p = 0.0216) suggesting a more favorable prognosis. Deficient mismatch repair (dMMR), associated with a favorable prognosis in different cancer types, was found in 4/39 (10%) MUC5AC positive cancers but in only 5/375 (1%) of MUC5AC negative cancers (p = 0.0052). In subgroup analyses MUC5AC positive endometroid carcinomas more frequently showed dMMR (4/10; 40%) as opposed to MUC5AC negative endometroid carcinomas (3/23; 13%; p = 0.0932). In summary, the results of our study show that MUC5AC expression is associated with mucinous and endometrioid ovarian carcinomas, lack of nodal metastases and dMMR. MUC5AC expressing ovarian cancers should be evaluated for dMMR.