Department of General, Visceral, and Transplant Surgery, University Hospital, LMU Klinikum, Ludwig-Maximilians-University Munich, Munich, Germany.
Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), University Hospital, LMU Klinikum, Ludwig-Maximilians-University of Munich, Munich, Germany.
J Cancer Res Clin Oncol. 2023 May;149(5):1895-1903. doi: 10.1007/s00432-022-04119-6. Epub 2022 Jul 7.
Small intestine neuroendocrine neoplasms (siNENs) will attain more importance due to their increasing incidence. Moreover, siNENs might lead to a desmoplastic reaction (DR) of the mesentery causing severe complications and deteriorating prognosis. The expression of fibrosis-related proteins appears to be the key mechanisms for the development of this desmoplastic reaction. Therefore, this study aimed to investigate the association of the desmoplastic mesentery with specific fibrosis-related protein expression levels.
By immunohistochemistry, the protein expression levels of four fibrosis-related markers (APLP2, BNIP3L, CD59, DKK3) were investigated in primary tumors of 128 siNENs. The expression levels were correlated with the presence of a desmoplastic reaction and clinico-pathological parameters.
In the primary tumor, APLP2, BNIP3L, CD59 and DKK3 were highly expressed in 29.7% (n = 38), 64.9% (n = 83), 92.2% (n = 118) and 80.5% (n = 103), respectively. There was no significant correlation of a single marker or the complete marker panel to the manifestation of a desmoplastic mesentery. The desmoplastic mesentery was significantly associated with clinical symptoms, such as flushing and diarrhea. However, neither the fibrosis-related marker panel nor single marker expressions were associated with clinical symptoms.
The expression rates of four fibrosis-related markers in the primary tumor display a distinct pattern. However, the expression patterns are not associated with desmoplastic altered mesenteric lymph node metastases and the expression patterns did not correlate with prognosis. These findings suggest alternative mechanisms being responsible for the desmoplastic reaction.
小肠神经内分泌肿瘤（siNENs）的发病率不断增加，其重要性也日益凸显。此外，siNENs 可能导致肠系膜发生纤维母细胞反应（DR），从而引发严重并发症，导致预后恶化。纤维化相关蛋白的表达似乎是发生这种纤维母细胞反应的关键机制。因此，本研究旨在探讨纤维母细胞反应性肠系膜与特定纤维化相关蛋白表达水平的相关性。
采用免疫组织化学法，检测 128 例 siNENs 原发肿瘤中四种纤维化相关标志物（APLP2、BNIP3L、CD59、DKK3）的蛋白表达水平，并将其与纤维母细胞反应的存在及临床病理参数进行相关性分析。
在原发肿瘤中，APLP2、BNIP3L、CD59 和 DKK3 的高表达率分别为 29.7%（n=38）、64.9%（n=83）、92.2%（n=118）和 80.5%（n=103）。单个标志物或完整标志物组与纤维母细胞反应性肠系膜的表现均无显著相关性。纤维母细胞反应性肠系膜与潮红和腹泻等临床症状显著相关，但纤维化相关标志物组或单个标志物的表达均与临床症状无关。
四种纤维化相关标志物在原发肿瘤中的表达率呈现出独特的模式。然而，这些表达模式与肠系膜纤维母细胞反应性转移淋巴结无关，且与预后无关。这些发现提示可能存在其他机制导致纤维母细胞反应。
