Van Laethem J L, Resibois A, Rickaert F, Devière J, Gelin M, Cremer M, Robberecht P
Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium.
Pancreas. 1997 Jul;15(1):41-7. doi: 10.1097/00006676-199707000-00006.
Pancreatic neoplasms harbor different prognoses according to their histological type: a benign course for serous cystadenoma, a low malignant potential for intraductal papillary mucinous neoplasms (IPMN), and high aggressiveness for ductal adenocarcinoma (ADC). Transforming growth factor beta 1 (TGF beta 1) may regulate tumor growth. The present study analyzes and compares the expression of its precursor beta 1-latency-associated peptide (beta 1-LAP), its latent binding protein (LTBP), and its mRNA in ductal adenocarcinoma (n = 10), in IPMN (n = 8), in serous cystadenoma (n = 2), and in normal tissues (n = 5). LTBP is thought to play a strategic role in the processing and active secretion of latent TGF beta 1 and its stockage in the extracellular matrix. Localization of beta 1-LAP and LTBP was assessed by immunohistochemistry using specific antibodies and expression of TGF beta 1 mRNA by reverse-transcriptase polymerase chain reaction analysis. beta 1-LAP was only slightly expressed in normal specimens, while LTBP was not detected. beta 1-LAP was detected in the cytoplasm of neoplastic cells in 9 of 10 patients with ADC. An intense staining was present in stromal cells surrounding the neoplastic glands in all cases except in one carcinoma in situ. LTBP was detected only in stromal cells and in the surrounding extracellular matrix. In IPMN with mild-grade dysplasia and in cystadenoma, beta 1-LAP was strongly expressed in the epithelial cells, while it was poorly detected in invasive IPMN; stromal cells were poorly or not all stained by beta 1-LAP, except in invasive IPMN (n = 2). LTBP was detected in neoplastic cells of three cases with benign IPMN and two of two cases with cystadenoma, while stroma was not immunostained. TGF beta 1 mRNA was strongly expressed in most of the tumors and no difference in expression was observed between the different types of neoplasms. There is no quantitative difference in expression of TGF beta 1 in ADC and in IPMN or cystadenoma. However, the latter are able to secrete TGF beta 1 efficiently, in contrast to ductal ADC as shown by the ability of the neoplastic cells to express both beta 1-LAP and LTBP. Invasive stroma reaction was associated with enhanced beta 1-LAP and LTBP expression in stromal cells and could be mediated by TGF beta 1 via LTBP
浆液性囊腺瘤病程良性，导管内乳头状黏液性肿瘤（IPMN）恶性潜能低，而导管腺癌（ADC）侵袭性高。转化生长因子β1（TGFβ1）可能调节肿瘤生长。本研究分析并比较了其前体β1-潜伏相关肽（β1-LAP）、潜伏结合蛋白（LTBP）及其mRNA在导管腺癌（n = 10）、IPMN（n = 8）、浆液性囊腺瘤（n = 2）和正常组织（n = 5）中的表达。LTBP被认为在潜伏性TGFβ1的加工、活性分泌及其在细胞外基质中的储存过程中起关键作用。使用特异性抗体通过免疫组织化学评估β1-LAP和LTBP的定位，并通过逆转录聚合酶链反应分析评估TGFβ1 mRNA的表达。β1-LAP在正常标本中仅轻度表达，而未检测到LTBP。在10例ADC患者中的9例肿瘤细胞胞质中检测到β1-LAP。除1例原位癌外，在所有病例中肿瘤腺体外围的基质细胞中均存在强染色。仅在基质细胞和周围细胞外基质中检测到LTBP。在轻度异型增生的IPMN和囊腺瘤中，β1-LAP在上皮细胞中强烈表达，而在侵袭性IPMN中检测较少；除侵袭性IPMN（n = 2）外，基质细胞被β1-LAP染色较弱或未全部染色。在3例良性IPMN和2例囊腺瘤的肿瘤细胞中检测到LTBP，而基质未被免疫染色。TGFβ1 mRNA在大多数肿瘤中强烈表达，不同类型肿瘤之间未观察到表达差异。ADC与IPMN或囊腺瘤中TGFβ1的表达无定量差异。然而，与导管ADC不同，后两者能够有效分泌TGFβ1，肿瘤细胞表达β1-LAP和LTBP的能力表明了这一点。侵袭性基质反应与基质细胞中β1-LAP和LTBP表达增强相关，可能由TGFβ1通过LTBP介导
