Kontogeorgos George
Department of Pathology and Pituitary Tumor Reference Center, G. Gennimatas General Hospital of Athens, Athens, Greece.
Neuroendocrinology. 2006;83(3-4):179-88. doi: 10.1159/000095526. Epub 2006 Oct 13.
The optimal goal for pathologists is to provide important information to clinicians in order to predict tumor biology. Specific morphologic features may serve as predictive markers of tumor behavior. Macroscopic invasion of the perisellar tissues, defined as radiographic or gross operative finding, is considered a more consistent prognostic indicator. Regarding morphology, cytologic atypia is not a reliable feature. In contrast, the number of mitoses is very important for prognosis. Given that only scarce mitoses can be identified in some aggressive cases, Ki-67 represents an alternative key feature to assess tumor proliferation. In the recent World Health Organization classification, the Ki-67 labeling index (LI) represents a major prognostic indicator for pituitary adenomas. Expression of the p53 gene product is very important for tumor biology. Adenomas with more than 3% Ki-67 LI and extensive p53 immunoreactivity are classified as 'atypical adenomas'. Apoptosis and mitoses represent two adverse and asynchronous events, maintaining the optimal cell numbers. Using DNA labeling techniques, we can identify apoptotic cells. A higher apoptotic LI was found in functioning compared with nonfunctioning adenomas, in microadenomas, particularly in corticotrope adenomas, and in untreated adenomas, particularly prolactinomas. Cytogenetic analysis of chromosomes may provide important information regarding tumor development and progression. Increased chromosome 11 copies are more frequent in functioning, aneuploid pituitary adenomas. Monosomy or partial loss of chromosome 11 in adenomas with a normal or increased DNA LI indicates complex genomic abnormalities of chromosomes, other than chromosome 11. Immunohistochemical detection of somatostatin receptors is important, as their density in the cytoplasmic membrane is directly related to the effectiveness of somatostatin analogues. Therefore, morphologic assessment of the somatostatin receptor profile can predict the responsiveness and validate the effectiveness of treatment with somatostatin analogues. We can conclude that among the currently available predictive factors, tumor invasiveness is important, whereas the presence of mitoses, the Ki-67 LI, p53 expression and apoptosis are very important; DNA ploidy and fluorescent in situ hybridization analysis, although important, are difficult to apply. Finally, in the near future, immunohistochemistry for somatostatin receptors will be a very important application.
病理学家的最佳目标是向临床医生提供重要信息，以便预测肿瘤生物学特性。特定的形态学特征可作为肿瘤行为的预测标志物。鞍周组织的宏观侵犯，定义为影像学或大体手术所见，被认为是一个更一致的预后指标。关于形态学，细胞异型性不是一个可靠的特征。相比之下，有丝分裂数量对预后非常重要。鉴于在一些侵袭性病例中只能识别出稀少的有丝分裂，Ki-67代表了评估肿瘤增殖的另一个关键特征。在最近的世界卫生组织分类中，Ki-67标记指数（LI）是垂体腺瘤的主要预后指标。p53基因产物的表达对肿瘤生物学特性非常重要。Ki-67 LI超过3%且p53免疫反应广泛的腺瘤被归类为“非典型腺瘤”。凋亡和有丝分裂代表两个不利且不同步的事件，维持着最佳细胞数量。使用DNA标记技术，我们可以识别凋亡细胞。与无功能腺瘤相比，在有功能腺瘤、微腺瘤（尤其是促肾上腺皮质激素腺瘤）以及未经治疗的腺瘤（尤其是泌乳素瘤）中发现凋亡LI更高。染色体的细胞遗传学分析可能提供有关肿瘤发生和进展的重要信息。在有功能的非整倍体垂体腺瘤中，11号染色体拷贝数增加更为常见。DNA LI正常或增加的腺瘤中11号染色体单体或部分缺失表明除11号染色体外的其他染色体存在复杂的基因组异常。生长抑素受体的免疫组织化学检测很重要，因为它们在细胞质膜中的密度与生长抑素类似物的有效性直接相关。因此，生长抑素受体谱的形态学评估可以预测反应性并验证生长抑素类似物治疗的有效性。我们可以得出结论，在目前可用的预测因素中，肿瘤侵袭性很重要，而有丝分裂的存在、Ki-67 LI、p53表达和凋亡非常重要；DNA倍体和荧光原位杂交分析虽然重要，但难以应用。最后，在不久的将来，生长抑素受体的免疫组织化学将是一个非常重要的应用。
