Université de Lyon 1, Université de Lyon, Lyon, France,
Faculté de Médecine Lyon-Est, Lyon, France,
Neuroendocrinology. 2019;109(1):70-76. doi: 10.1159/000499382. Epub 2019 Apr 3.
The behaviour of lactotroph tumours varies between benign tumours, those cured by treatment, and that of aggressive tumours, and carcinomas with metastasis. Identification of clinical, pathological and molecular factors is essential for the early identification of patients that may have such aggressive tumours. Plasma prolactin levels and tumour size and invasion, per se, are not prognostic factors. However, tumours appearing at a young age (<20 years), especially in boys, and the presence of genetic predisposition have a poorer prognosis. In addition, lactotroph tumours in men differ from those in women, being larger, more often invasive, and resistant to dopamine agonists. They are also more often high-grade with a high risk of recurrence and malignancy. The expression of estrogen receptor α is lower than in women and is closely correlated to aggressiveness. Proliferation markers (Ki-67 expression: ≥3%, mitotic count n > 2) are correlated to invasion and proliferation, but, taken alone, their prognostic value is debatable. Based on a 5-tiered clinicopathological classification, and taking into account invasion and proliferation, a grade 2b (aggressive) lactotroph tumour has a 20× risk of progression compared to a grade 1a (benign) tumour. Moreover, lactotroph tumours are the second-most frequent aggressive and malignant tumour. Other factors, such as the expression of growth factors (vascular endothelial growth factor [VEGF] and epidermal growth factor [EGF]), the genes regulating invasion, differentiation and proliferation, adhesion molecules (E-cadherin), matrix metalloproteinase 9, and chromosome abnormalities (chromosomes 11, 19, and 1), have also been correlated with aggressiveness. Currently, clinical signs, a prognostic classification, and molecular and genetic markers may all help the clinician in the early identification of aggressive lactotroph tumours and enable stratification of their management.
催乳素细胞瘤的行为在良性肿瘤、可通过治疗治愈的肿瘤和侵袭性肿瘤以及有转移的癌之间有所不同。识别临床、病理和分子因素对于早期识别可能具有侵袭性肿瘤的患者至关重要。血浆催乳素水平和肿瘤大小及侵袭性本身并不是预后因素。然而，年龄较小（<20 岁），尤其是男孩，以及存在遗传易感性的肿瘤，预后较差。此外，男性的催乳素细胞瘤与女性不同，它们更大，更常侵袭，并且对多巴胺激动剂有抗性。它们也更常为高级别，具有较高的复发和恶性风险。雌激素受体 α 的表达低于女性，并且与侵袭性密切相关。增殖标志物（Ki-67 表达：≥3%，有丝分裂计数 n>2）与侵袭和增殖相关，但单独来看，其预后价值存在争议。基于 5 级临床病理分类，并考虑到侵袭和增殖，与 1a 级（良性）肿瘤相比，2b 级（侵袭性）催乳素细胞瘤的进展风险增加 20 倍。此外，催乳素细胞瘤是第二常见的侵袭性和恶性肿瘤。其他因素，如生长因子（血管内皮生长因子[VEGF]和表皮生长因子[EGF]）、调节侵袭、分化和增殖的基因、黏附分子（E-钙黏蛋白）、基质金属蛋白酶 9 和染色体异常（染色体 11、19 和 1）的表达也与侵袭性相关。目前，临床症状、预后分类以及分子和遗传标志物都可能有助于临床医生早期识别侵袭性催乳素细胞瘤，并对其管理进行分层。
