Ten of the remaining 17 undifferentiated carcinomas showed the following alterations: 5 tumors (15%) showed loss of ARID1A only with intact ARID1B, BRG1, and INI1 expression, 4 tumors (12%) showed mutated patterns of p53 staining with intact SWI/SNF protein expression, and 1 tumor (3%) harbored a POLE exonuclease domain mutation (P286R).
According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: (a) hypermutated tumors with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%); and (d) low copy number alterations (copy-number low) tumors with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%).
The positive rate of p21 in GC was lower than that in NGM and DP (P<0.05), while the positive rate of p53 in GC was higher than that in NGM and DP (P<0.05). p21 and p53 were significantly expressed in 63.3% (19/30) and 36.7% (11/30), 35.0% (14/40) and 77.5% (31/40), 26.7% (4/15) and 80.0% (12/15), 30.8% (4/13) and 30.8% (4/13), and 20.0% (2/10) and 30.0% (3/10) of well-differentiated, poorly-differentiated, undifferentiated carcinomas, mucoid carcinomas and signet ring cell carcinomas.
These facts indicate that an N-ras mutation may induce follicular neoplasm and a subsequent p53 mutation may have caused the follicular neoplasm to transform to anaplastic carcinoma in this patient.
Considering that TCIC is intermediate between papillary plus follicular carcinoma and anaplastic carcinoma in terms of survival and the rate of mutation of the p53 gene, we can speculate that mutation in the p53 gene might be associated with the insular component and might play an important role in the clinicopathological behavior of thyroid carcinoma.
While 30 of 32 (94%) cases in differentiated nonkeratinizing carcinoma (NKC, WHO type 2) and 16 of 17 (94%) cases in undifferentiated carcinoma (UC, WHO type 3) showed EBERs expression, neither five cases of keratinizing squamous cell carcinoma (KSCC, WHO type 1) nor two cases of adenocarcinoma showed EBERs. bcl-2 protein was detected in 50 (89%) cases, but its expression did not depend on expression of LMP1. p53 protein was detected in 31 (55%) cases, and there was a correlation between expression of EBERs and p53 protein (P < 0.05) but not between LMP1 and p53 protein.
A series of 74 esophageal carcinomas (46 squamous cell carcinomas, 21 Barrett's adenocarcinomas, and 7 undifferentiated carcinomas) was studied by single strand conformation polymorphism (SSCP) analysis and immunohistochemistry (IHC) to detect p53 mutation and accumulation, respectively.
Our results suggest that in tumours of the follicular epithelium p53 and bcl-2 protein abnormalities are associated with more advanced carcinomas and especially with undifferentiated carcinomas, while they are only rarely altered in tumours of the parafollicular C cells.
The results suggest positivity in nucleus staining for p53 may be a marker for the biologically worse carcinomas, PDC and UDC, however, tumors showing only cytoplasmic staining of p53 favor a fair prognosis.
These results that p16/CDKN2 gene alteration is not required for malignant transformation in the thyroid, while p53 gene mutations may play a role in the progression from differentiated to undifferentiated carcinoma.
The results imply that LOH occurs first in papillary adenocarcinoma followed by a p53 mutation during the transition from papillary adenocarcinoma to undifferentiated carcinoma.
These results indicate that mutations of the p53 gene are associated with the most aggressive histologic types of thyroid tumors, such as the undifferentiated carcinoma and, to a certain extent, the poorly differentiated carcinoma, and that the alterations of this gene represent a late genetic event in human thyroid carcinogenesis.