To determine estrogen as a growth promotor, the authors investigated the presence or absence of estrogen receptor-alpha (ER-alpha), ER-beta, progesterone receptor, and dioxin receptor (i.e., aromatic hydrocarbon receptor) in clinically resected ovarian CCA, serous adenocarcinoma (SAC), endometrioid adenocarcinoma (EAC), and mucinous adenocarcinoma (MAC) specimens using an immunohistochemical method.
Of the 18 ALK fusion-positive lung adenocarcinomas, 8 cases (44.4%) were histologically diagnosed as subtypes of cribriform adenocarcinoma, 7 cases (38.9%) as cribriform adenocarcinoma mixed with papillary and/or mucinous pattern, 2 cases (11.1%) as papillary adenocarcinoma, and 1 case (5.6%) as mucinous adenocarcinoma.
In conclusion, aberrant ALK expression is observed in ovarian serous carcinoma but not in mucinous carcinoma, is independent of gene translocation, and might be associated with progression and prognosis.
Among the 897 non-mucinous adenocarcinomas, 61 PMPA with ≤90% mucin and 39 PMPA with >90% mucin, ALK rearrangements were found in 47 (5.2%) non-mucinous adenocarcinomas, 9 (14.8%) PMPA with ≤90% mucin and 12 (30.8%) PMPA with >90% mucin, respectively, with an ordinal association (coefficient, 95% CI=0.11, 0.06 to 0.17).
Pulmonary invasive mucinous adenocarcinomas and mixed nonmucinous/mucinous adenocarcinomas are clinically and genetically similar, except for a higher rate of ALK rearrangement in mixed tumors.
To examine the relationship between subsets of colorectal polyps and non-mucinous and mucinous adenocarcinomas of the colorectum, we evaluated the frequency of the expression of cell lineage associated mucin core proteins (MUC5AC and MUC2), trefoil factors (TFF1 and TFF3), and APC and p21 in these tissues.
APC inactivation and K-ras mutations occurred more frequently in NMC (APC, 88%, p<0.001; K-ras, 58%, p=0.01) than in MC (APC, 24%; K-ras, 28%) regardless of MSI status.
ARID1A-deficient tumors showed a strong correlation with a medullary and mucinous phenotype, and 8 of 12 (67%) had at least one feature reminiscent of high microsatellite instability colon carcinomas (mucinous or medullary differentiation, marked intratumoral or peritumoral lymphoid infiltrate).
In conclusion, the Atoh1 protein regulates malignant potential rather than the differentiation phenotype of MC, suggesting the mechanism by which MC and SRCC are more malignant than non-mucinous adenocarcinoma.
In univariate analysis, histology (NMA vs. MA/MC), American Joint Committee on Cancer stage (IIIA, IIIB, and IIIC), and lymphovascular invasion (present vs. absent) were significantly associated with DFS.
The group of mucinous carcinomas demonstrated both MYC DNA amplification and strong bcl-2 expression in 50% and contained the largest fraction of cases without aberration (37.5%).
Hierarchical clustering isolated three relevant clusters: (i) cluster of microsatellite stable mucinous adenocarcinomas (54%) with KRAS mutation, and frequent MGMT changes, more frequently located in the left colon, often associated with contiguous precursor adenoma; (ii) cluster of BRAF-mutated mucinous adenocarcinomas (28%) with either microsatellite instability-high or microsatellite stable status, occurring in elderly female patients, nearly all located in the right colon, having the signature of serrated pathway of carcinomas; and (iii) a heterogeneous cluster of microsatellite instability-high mucinous carcinomas (18%), including inherited colorectal carcinomas, displaying a high-grade histological pattern.
The application of mutation analysis of the KRAS and BRAF genes (members of the RAS-RAF-MEK-ERK-MAP kinase pathway) is consistent with the model for progression of mucinous carcinomas and a subset of serous carcinomas (the so-called low-grade serous carcinomas) through benign and borderline lesions.
A deficient mismatch repair system and BRAF mutations were observed in 17% and 22% of patients with MC, compared to 3% and 7% in patients with AC, respectively.
The 3 MSI-high cases included: (1) a poorly differentiated nonmucinous adenocarcinoma with loss of MLH1/PMS2 expression, lack of MLH1 promoter methylation, and lack of BRAF gene mutation, but no detected germline mutation in MLH1 from a 39-year-old man; (2) an undifferentiated carcinoma with loss of MSH2/MSH6, but no detected germline mutation in MSH2 or TACSTD1, from a 59-year-old woman; and (3) a moderately differentiated mucinous adenocarcinoma arising in a villous adenoma with loss of MSH2/MSH6 expression, in a 38-year-old man with a strong family history of CRC who declined germline testing.
High-level microsatellite instability, CpG island methylation phenotype-positive status and BRAFV600E mutation were more often seen in signet ring cell carcinoma and mucinous adenocarcinoma compared with conventional adenocarcinoma.
In conclusion, alteration of BRCA-1 expression is more frequent in serous than in mucinous carcinomas and is associated with tumors of higher grades and high proliferation rate.