p53 Protein, PCNA staining, and DNA content in follicular neoplasms of the thyroid gland

Abstract

Forty-nine follicular adenomas and 11 follicular carcinomas of the thyroid were investigated by immunohistochemistry for the expression of p53 protein and proliferating cell nuclear antigen (PCNA). The DNA ploidy and the S-phase fraction (SPF) of the neoplasms were analysed by flow cytometry. Twelve adenomas (24 per cent) and six carcinomas (55 per cent) were DNA non-diploid (P = 0.07). The carcinomas had a higher proliferation rate than the adenomas when assessed either by SPF size (median 9.9 per cent vs. 2.9 per cent, P = 0.0003) or by PCNA staining intensity (P < 0.0001). Some scattered nuclei in two (4 per cent) adenomas and in three (27 per cent) carcinomas stained positively for p53 (P = 0.04). The two adenomas with positive staining for p53 were subserially sectioned, but no signs of invasion were found; both patients are alive and well 6 and 7 years after surgery. One of the two adenomas showing positive p53 nuclear staining was DNA aneuploid, and both were positive in PCNA staining, but their SPFs were low (2.1 and 3.3 per cent). We conclude that p53 protein expression is not confined to follicular carcinomas; scattered p53-positive cells may also be present in histologically and clinically benign follicular adenomas. Because both follicular adenomas and carcinomas may be DNA aneuploid and their SPF and PCNA staining distributions overlap, the distinction between follicular adenoma and carcinoma should still be based on histological criteria.

Comparative Analysis of Protein Expression in Differentiated Thyroid Tumours: A Multicentre Study

“…The most frequently detected mutations in human malignancy involve the cell-cycle control factors p53, PCNA and Ki-67. 11,12 In the present study there was significantly higher expression of p53 and PCNA in thyroid carcinomas compared with thyroid adenomas, however the expression of Ki-67 was not significantly different Tissue microarrays for immunohistochemistry were constructed using 119 thyroid tumour samples (papillary carcinomas, n = 45; follicular carcinomas n = 26; and adenomas, n = 48). ROC AUC, receiver-operating characteristic area under the curve; CI, confidence interval; MMP, metalloproteinase; HBME-1, Hector Battifora mesothelial-1; FHIT, fragile histidine triad.…”

Cell proliferation marker MCM2, but not Ki67, is helpful for distinguishing between minimally invasive follicular carcinoma and follicular adenoma of the thyroid

“…Although neither architectural nor cytological features are reliable criteria for a diagnosis of MIFC versus FA, 1 there may be a difference in the proliferative potential of the tumour cells. Various proliferation markers such as Ki67, 9–16 proliferating cell nuclear antigen (PCNA) 17–21 and argyrophilic nucleolar organizer regions (AgNORs) 15,21 , 22 have been examined in thyroid tumours, some being reported to be useful for differential diagnosis between follicular carcinoma and FA 10,11 , 15–21 . Minichromosome maintenance protein (MCM) 2 is a member of the six MCM protein family and serves as a ‘licensing factor’ for cell cycle progression, playing a direct role in the initiation of DNA synthesis at replication and limiting replication after completing one cell cycle 23–25 .…”

Hyalinizing Trabecular Adenoma of the Thyroid

“…4 The high expression of PCNA in our three HTAs was unusual for a benign thyroid neoplasm, but it does not help in their differentiation from malignant thyroid tumors.…”