Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in gastrointestinal carcinoids
Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in gastrointestinal carcinoids
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DOI：
10.1097/00000478-199703000-00009
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发表时间：
1997-03-01
影响因子：
5.6
通讯作者：
Dayal, Y
中科院分区：
文献类型：
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作者：
Krishnamurthy, S;Dayal, Y
转化生长因子- α (tgf - α)是一种强效生长因子，属于表皮生长因子家族，通过与表皮生长因子受体（EGFR）结合，在正常细胞和肿瘤细胞的增殖和分化中发挥作用。tgf - α和EGFR在肿瘤中的共表达被认为赋予肿瘤细胞生长优势。为了评估它们在胃肠道（GI）类癌等惰性肿瘤中的作用，我们研究了tgf - α和EGFR在25个胃肠道类癌（9个前肠、13个中肠和3个后肠）中的免疫组织化学表达，并研究了它们的表达与这些肿瘤的分泌和临床病理特征的相关性。这些肿瘤中有18例（72%）表达tgf - α， 17例肿瘤中有16例显示EGFR细胞外结构域的免疫阳性，而没有一例表达其细胞内结构域。10例tgf - α阳性肿瘤血清素阳性，7例生长抑素阳性，3例降钙素阳性，胃泌素、胰高血糖素、胰多肽、血管活性肠肽和生长激素释放因子各1例。7例tgf - α阳性肿瘤为多激素肿瘤，8例为单激素肿瘤，3例对所研究的调节物质完全无反应。除了与肿瘤细胞5-羟色胺（5-羟色胺）的表达相关外，tgf - α：的表达与肿瘤的起源部位、大小、壁内浸润深度、转移和分泌谱等其他病理特征无显著相关性。这些发现表明，尽管tgf - α在胃肠道类癌中表达的比例很高，但肿瘤细胞上缺乏其完整的受体分子（EGFR），使其作为生长因子的功能无效。因此，与胃肠道癌不同，tgf - α似乎在胃肠道类癌的生长和进展中没有作用，这可能解释了胃肠道类癌的惰性行为和缓慢的生物学进展。
Transforming growth factor-alpha (TGF-alpha), a potent growth factor belonging to the epidermal growth factor family, exerts its role in the proliferation and differentiation of normal and neoplastic cells by binding to epidermal growth factor receptor (EGFR). Coexpression of TGF-alpha and EGFR in carcinomas is believed to confer growth advantage to tumor cells. To evaluate their role in such indolent tumors as gastrointestinal (GI) carcinoids, we investigated the immunohistochemical expression of TGF-alpha and EGFR in 25 GI carcinoids (nine foregut, 13 midgut, and three hindgut) and studied the correlation of their expression with the secretory and clinicopathologic profiles of these tumors. TGF-alpha was expressed in 18 (72%) of these tumors, and whereas 16 of 17 tumors showed immunopositivity for the extracellular domain of EGFR, none expressed its intracellular domain. Ten TGF-alpha-positive tumors were positive for serotonin, seven for somatostatin, three for calcitonin, and one tumor each for gastrin, glucagon, pancreatic polypeptide, vasoactive intestinal peptide, and growth hormone-releasing factor, respectively. Seven TGF-alpha-positive tumors were multihormonal, eight were monohormonal, and three were completely nonreactive for the regulatory substances studied. Except for its correlation with 5-hydroxytryptamine (serotonin) expression by the tumor cells, expression of TGF-alpha: showed no significant association with other pathologic attributes, for example, the site of origin, size, depth of intramural penetration, metastases, and the secretory profiles of the tumors. These findings indicate that although TGF-alpha is expressed by a high proportion of GI carcinoids, the absence of its intact receptor molecule (EGFR) on the tumor cells renders it functionally ineffective as a growth factor. Thus, unlike in carcinomas of the GI tract, TGF-alpha appears to play no role in the growth and progression of GI carcinoids, which perhaps explains the indolent behavior and slow biological progression of GI carcinoids.