Evaluation of Retinoblastoma and Ki‐67 Immunostaining as Diagnostic Markers of Benign and Malignant Parathyroid Disease

Abstract

Assessment of the malignant potential of parathyroid tumors in the absence of metastases can be difficult using morphologic criteria alone. In this study we have examined a total of 58 parathyroid tumors (31 benign, 15 malignant, and 12 equivocal) from 54 patients using immunohistochemistry with monoclonal antibodies directed against the retinoblastoma (RB) protein and the cell cycle-associated antigen Ki-67 to evaluate their role as diagnostic markers. RB protein immunoreactivity was not useful for distinguishing between benign and malignant parathyroid tumors. Analysis of the proliferation marker Ki-67 showed that there was a trend toward more intense staining in the malignant cases. The Ki-67 labeling index was highest in the parathyroid cancers (median 33) and lowest in the sporadic primary adenomas (median 2). An observation that might have clinical implications is that tumors from patients with familial hyperparathyroidism linked to chromosome 1q showed a high Ki-67 index, indicating strong proliferative activity (median 25). This correlates well with the clinical observation of tumors with malignant potential in this syndrome. Because of the considerable overlap between groups of tumors, Ki-67 is not suitable for definitive differentiation between benign and malignant tumors. However, Ki-67 may give valuable information about which patients should be followed more closely.;1999>

Loss of Parafibromin Immunoreactivity Is a Distinguishing Feature of Parathyroid Carcinoma

“…Levin (40) distinguished between "typical" and "atypical adenomas." Others have chosen to label this group as "equivocal carcinomas" (22,28). We prefer the terminology "equivocal carcinoma" in the research and clinical setting, as gold-standard pathologic criteria does not accommodate a localized parathyroid carcinoma (2,27,40).…”

“…Studies of pRb immunostaining have also yielded conflicting results. Some studies have reported that it may be a helpful marker (25,26), but several other studies have contradicted these findings (22,23). A recent review of RB gene abnormalities in parathyroid carcinoma concluded that no definitive conclusion could be drawn with regards to pRb staining (26).…”

“…In all cases (both full sections and arrays), lesions were diagnosed as definite carcinomas only if vascular invasion, invasion of surrounding tissue, or distant metastasis were evident. Equivocal carcinomas were defined as tumors exhibiting histopathologic features of carcinoma without the presence of vascular invasion, invasion of surrounding tissue, or distant metastasis (22,28). Clinicopathologic data for the definite and equivocal carcinoma cases, following reclassification as described below, are shown in Table 1.…”

Diagnosis of parathyroid carcinoma using immunohistochemical staining against hTERT

“…However, the abnormality of p53 gene expression was found to vary (0-100%) in carcinomas (10)(11)(12)16,27). In addition to the p53 abnormality, the loss of Rb (11,14) and p21 (16) expression, and the accumulation of cyclin D1 (16) and p27 (28) expression suggest a disintegration of the cell cycle control, although this was not always present (up to 55%). The accelerated cell proliferation in carcinoma was successfully evaluated by displaying the increase in PCNA- (15) or the Ki-67-positive cell population.…”

“…However, a consensus has yet to be reached in identifying parathyroid carcinoma from adenoma using these markers. Only Ki-67 demonstrated a universally accepted clinical significance (10)(11)(12)(13)(14). However, several falsepositive and false-negative results in diagnosis have been reported (10,11,15,16).…”