Expression of Mcl-1 and Ki-67 in Papillary Thyroid Carcinomas.
Studying molecules that are differentially expressed in cancers as well as benign and normal tissues is crucial for identifying novel biomarkers for cancer immunotherapy. This study aimed to investigate the clinical utility of the immunochemical expression of the proliferative cell marker Ki-67 and the apoptotic blocker Mcl-1 in papillary thyroid carcinoma (PTC).


METHODS
We built a tissue microarray with 282 thyroid specimens. There were 59 PTCs including 35 classic (CPTC), 3 tall cell (TCPTC) and 21 follicular variants (FVPTC); 79 benign thyroid diseases (22 follicular adenomas; 57 adenomatoid hyperplasia); 33 Hashimoto's thyroiditis (HT) specimens; and 111 normal thyroid tissues. Clinical history and ultrasound data were retrospectively obtained by chart review.


RESULTS
Mcl-1 overexpression was evident in 66.7% of the PTC tissues compared to 32% of the benign thyroid diseases. Mcl-1 strong staining distinguished benign from malignant thyroid lesions (sensitivity=61.3%; specificity=72.8%; negative predictive value, NPV=68%; positive predictive value, PPV=66.7% and 67.5% accuracy). Positive nuclear Ki-67 staining was observed in 34% of PTCs vs. 19% of thyroid adenomas (P=0.031). Strong Mcl-1 and Ki-67 co-expression was identified in 57.5% of PTCs with a higher PPV (75.8%). Mcl-1 and Ki-67 expression was not associated with any clinicopathological feature of malignancy. No deaths occurred during the follow-up.


CONCLUSIONS
Mcl-1 immunochemical overexpression allowed differentiating low-risk PTC from the benign thyroid lesions. We suggest that Mcl-1 expression may help differentiate follicular patterned thyroid lesions. The influence of the Mcl-1 expression on several features of tumor aggressiveness has to be studied in large series of high-risk thyroid carcinomas.
Endocrinology Division, Department of Internal Medicine, University of Campinas, São Paulo, Brazil.
F F R
FF
Maia
Department of Pathology, Medical Science School, University of Campinas, São Paulo, Brazil.
J
J
Vassallo
Laboratory of Specialized Pathology, CAISM, University of Campinas, São Paulo, Brazil.
G A
GA
Pinto
Endocrinology Division, Department of Internal Medicine, University of Campinas, São Paulo, Brazil.
E J
EJ
Pavin
Department of Pathology, Medical Science School, University of Campinas, São Paulo, Brazil.
P S
PS
Matos
Endocrinology Division, Department of Internal Medicine, University of Campinas, São Paulo, Brazil.
D E
DE
Zantut-Wittmann
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein