Cytoplasmic OCT4 Staining Is a Sensitive and Specific Marker of Neuroendocrine Differentiation
Riley E Alexander, David J Grignon, Liang Cheng, Muhammad T Idrees. Indiana University School of Medicine, Indianapolis, IN
Background: OCT4 is a transcription factor that has gained wide clinical usage as a diagnostic marker in the setting of germ cell tumors. A previous study by the authors described a novel cytoplasmic staining pattern in normal adrenal medullary tissue and pheochromocytomas. Ultrastructural studies performed at that time showed the antibody binding to neurosecretory granules (NSGs). From this, we hypothesized that similar staining may be detected in other neuroendocrine tissues. The goal of this study is to test this hypothesis by examining a wide array of neuroendocrine tumors for the presence of this novel cytoplasmic staining pattern.
Design: 49 cases of neuroendocrine tumors were selected from our institution's case files. These consisted of 26 cases classified as well-differentiated, 6 moderately differentiated, and 17 cases of small cell or high grade neuroendocrine carcinoma. All cases were immunostained with OCT4 and Ki-67. OCT4 reactivity was then scored for intensity (0-3+) and extent (0-3+). Ki-67 proliferation index was scored as a percentage of total tumor cells. Immunoelectronmicroscopy (IEM) was performed to determine precise location of antibody binding within cells.
Results: Immunoreactivity was seen in 24 of 26 (92%) cases of carcinoid tumors. 23 of these 24 (96%) cases showed strong reactivity (2-3+ intensity and extent). The same type of strong staining was seen in 4 of 6 (67%) moderately differentiated neuroendocrine tumors. Only 2 of 17 (12%) cases of high grade neuroendocrine carcinoma cases showed similar staining. A strong, inverse correlation was seen with OCT4 staining intensity and degree of differentiation (correlation coefficient of -0.73). The same correlation was seen with regards to OCT4 staining and Ki-67 index. IEM showed binding of OCT4 antibody to neurosecretory granules.
Conclusions: Cytoplasmic staining of OCT4 is a sensitive and specific marker of neuroendocrine differentiation. These findings expand those of our previous work and assert that this particular antibody has a high affinity for neuroendocrine tissue. This report also shows that as neuroendocrine tumors become less differentiated and lose their cytoplasm and, therefore its contents (i.e., NSGs), OCT4 staining decreases accordingly. Though further validation is necessary, OCT4 may prove to be a clinically useful immunostain in the diagnosis of neuroendocrine tumors. Furthermore, the loss or depletion of immunoreactivity in higher-grade tumors may provide an adjunct for classification in difficult cases with limited tissue available.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 79, Monday Morning