Hosny Mohammed Kareem, Siddiqui Momin T, Willis Brian C, Zaharieva Tsvetkova Dobromira, Mohamed Amr, Patel Snehal, Sharma Jyotirmay, Weber Collin, Cohen Cynthia
Departments of *Cardiology ‡Pathology and Laboratory Medicine ∥Surgery, Emory University School of Medicine §Department of Medicine, Morehouse School of Medicine, Atlanta, GA †Medical Research Division, National Research Center, Cairo, Egypt.
Appl Immunohistochem Mol Morphol. 2017 Nov/Dec;25(10):731-735. doi: 10.1097/PAI.0000000000000378.
Differentiation of parathyroid carcinoma (PC) from parathyroid adenoma (PA) relies solely on the pathologic determination of invasion of surrounding structures and/or distant metastasis. Parathyroid lesions with atypical histologic features with no demonstration of invasion or metastasis present a diagnostic dilemma. Different authors report a parafibromin and adenomatous polyposis coli (APC) loss or reduction in PC cases. High proliferative activity of MIB-1 and increased galectin 3 expression are reported in PC. There is no clear cutoff for the sensitivity, specificity, or predictive value for all these markers.
The immunohistochemical expression of parafibromin, APC, MIB-1, and galectin 3 was studied in 73 adenomas, 21 PCs, and 3 atypical adenomas. The presence or absence of each marker was identified through the use of a comprehensive scoring system based on multiplying the percentage of tumor cells stained (0 to 100) and the staining intensity (0 to 3) on each biopsy. The highest score that any slide could reach was 300. A cutoff of >100 was used to consider the specimen positive for parafibromin, APC, or galectin 3 staining. MIB-1 proliferation indices were calculated using image cytometry; proliferation indices >5% were considered positive.
We identified parafibromin loss in 7/21 (33%) carcinomas and 1/73 (1%) adenomas. Loss of APC was seen in 20/21 (95%) carcinomas and 38/73 (52%) adenomas. MIB-1 indices were elevated in 18/21 (86%) carcinomas. MIB-1 indices were <5% in all (100%) adenomas. MIB-1 indices were elevated in 2/3 (67%) atypical adenomas.
Our study presents a clear cutoff to determine the practicality of using parafibromin, APC, and MIB-1 as immunohistochemical markers to differentiate between PCs and PAs. Loss of parafibromin and a high MIB-1 index are both independently sensitive and specific markers for the diagnosis of PC. Loss of APC was only specific for PC. This panel of markers provides a novel, useful approach in the diagnosis and differentiation of PCs from PAs.
甲状旁腺癌（PC）与甲状旁腺腺瘤（PA）的鉴别仅依赖于对周围结构侵犯和/或远处转移的病理判定。具有非典型组织学特征但无侵犯或转移证据的甲状旁腺病变存在诊断难题。不同作者报道在PC病例中存在副纤维蛋白和腺瘤性息肉病基因（APC）缺失或减少。据报道PC中MIB - 1的高增殖活性及半乳糖凝集素3表达增加。对于所有这些标志物，其敏感性、特异性或预测价值均无明确的临界值。
研究了73例腺瘤、21例PC和3例非典型腺瘤中副纤维蛋白、APC、MIB - 1和半乳糖凝集素3的免疫组化表达。通过使用基于将肿瘤细胞染色百分比（0至100）与每次活检的染色强度（0至3）相乘的综合评分系统来确定每种标志物的有无。任何一张切片能达到的最高分是300分。副纤维蛋白、APC或半乳糖凝集素3染色的标本，若得分>100分则判定为阳性。使用图像细胞术计算MIB - 1增殖指数；增殖指数>5%被视为阳性。
我们发现7/21（33%）例癌中存在副纤维蛋白缺失，73例腺瘤中有1/73（1%）例存在缺失。20/21（95%）例癌中可见APC缺失，73例腺瘤中有38/73（52%）例存在缺失。18/21（86%）例癌中MIB - 1指数升高。所有腺瘤（100%）的MIB - 1指数均<5%。2/3（67%）例非典型腺瘤中MIB - 1指数升高。
我们的研究给出了一个明确的临界值，以确定使用副纤维蛋白、APC和MIB - 1作为免疫组化标志物来鉴别PC和PA的实用性。副纤维蛋白缺失和高MIB - 1指数均是诊断PC的独立敏感且特异的标志物。APC缺失仅对PC具有特异性。这组标志物为PC与PA的诊断和鉴别提供了一种新的、有用的方法。
