Class III beta-tubulin isotype (beta III) in the adrenal medulla: II. Localization in primary human pheochromocytomas.
The Class III beta-tubulin isotype (beta III) is expressed specifically in central and peripheral nervous system neurons at various stages of neuronal differentiation. We have shown previously that beta III is expressed in a differentiation-dependent manner in human neuroblastomas arising in the adrenal medulla and sympathetic chains (Katsetos et al., Clin Neuropathol 13:241-255, 1994). The neuronal distribution of beta III in the developing and mature human adrenal medullae is detailed in the companion article (Katsetos et al., 1998A).



We have compared the localization of the neuronal beta III to S-100 protein, a sustentacular cell marker, in 14 formalin-fixed, paraffin-embedded primary human pheochromocytomas of the adrenal medulla and 14 adrenocortical tumors (adenomas and carcinomas).



In pheochromocytomas, beta III staining was present in all tumors, but the number of stained cells varied in the two neural neoplastic phenotypes. Although the majority of chromaffin-like cells were beta III-positive, there was a lack of beta III in one-third of the tumor cells. Compared to chromaffin-like phenotypes, neuronal (ganglion-like cells) were invariably beta III-positive. Stromal sustentacular cells, stromal fibroblasts, and tumor blood vessels were beta III-negative. Sustentacular cells in pheochromocytomas were S-100 protein-positive, but beta III-negative. Primary adrenocortical tumors were beta III-negative with the exception of rare beta III-positive cells demonstrated in one case.



The distribution of beta III in human pheochromocytomas of the adrenal gland is differentiation-dependent, closely recapitulating chromaffin cell and neuronal phenotypes of the normal adrenal medulla. Our findings indicate that beta III may be used as one of the adjuvant neural markers in the differential diagnosis of adrenal tumors, i.e., pheochromocytoma versus adrenocortical carcinoma. The occurrence of rare beta III-positive cells in cortical carcinomas is exceptional and probably represents the acquisition of a divergent neuroendocrine phenotype. The significance of the latter is unclear, although it may constitute a marker for malignancy.
Karkavelas
G
G
Neuropathology Laboratory, Hahnemann University, Philadelphia, Pennsylvania, USA.
Katsetos
C D
CD
Geddes
J F
JF
Herman
M M
MM
Vinores
S A
SA
Cooper
H S
HS
Provencio
J
J
Frankfurter
A
A
D000306:Adrenal Cortex Neoplasms / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000313:Adrenal Medulla / Q000378:metabolism*; D000328:Adult; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007536:Isomerism; D008297:Male; D010673:Pheochromocytoma / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism; D014018:Tissue Distribution; D014404:Tubulin / Q000378:metabolism*
D009418:S100 Proteins; D014404:Tubulin