Fiocca R, Rindi G, Capella C, Grimelius L, Polak J M, Schwartz T W, Yanaihara N, Solcia E
Regul Pept. 1987 Jan;17(1):9-29. doi: 10.1016/0167-0115(87)90029-2.
Glucagon/PP-related peptides were detected immunohistochemically in 18 out of 22 cases of rectal tumors investigated. The reactive tumors showed prevalence of trabecular or mixed trabecular-acinar structure and moderate staining with Grimelius' silver and lead-hematoxylin. Three of the remaining 4 cases were characterized by reactivity for 5-hydroxytryptamine only, prevalence of a solid nest structural component and intense staining with Grimelius' silver technique and lead-hematoxylin. Fifteen of the 18 glucagon/PP-reactive cases were investigated immunohistochemically with a series of 6 sera directed against different sequences of glucagon, glicentin and proglucagon, and of 7 sera directed against PP, PYY and proPP-icosapeptide. A large spectrum of glucagon-related immunoreactivities, including C-terminus and mid-portion glucagon-immunoreactivity, N- and C-terminus glicentin-immunoreactivity, GLP1- and GLP2-immunoreactivity, were detected in human rectal L cells and most rectal carcinoids. With the exception of a few scattered cells in the rectal mucosa and in 3 tumors, C-terminus glucagon-immunoreactivity was obtained only after trypsin or subtilisin treatment of tissue sections. Both PYY and PP/proPP-like peptide(s) were detected in rectal L cells and carcinoids, with prevalence of PYY in normal cells and PP/proPP-like peptides in tumor cells. It is concluded that the same or closely related hormone/prohormone sequences are synthesized and stored in rectal endocrine cells and carcinoid tumors although differences of quantitative expression, post-translational cleavage or reactivity to antibodies may occur. The usefulness of protease treatments of tissue sections to unmask immunoreactivities of uncleaved propeptides or fixative-denatured peptides is outlined.
在研究的22例直肠肿瘤中,有18例通过免疫组织化学检测到胰高血糖素/胰多肽相关肽。反应性肿瘤表现为小梁状或混合小梁状-腺泡状结构,用格里梅利乌斯银染法和铅苏木精染色呈中度染色。其余4例中有3例仅对5-羟色胺有反应性,以实性巢状结构成分占优势,用格里梅利乌斯银染法和铅苏木精染色呈强阳性。对18例胰高血糖素/胰多肽反应性病例中的15例,用一系列6种针对胰高血糖素、肠高血糖素和胰高血糖素原不同序列的血清,以及7种针对胰多肽、肽YY和胰多肽前体-icosapeptide的血清进行免疫组织化学研究。在人直肠L细胞和大多数直肠类癌中检测到了广泛的胰高血糖素相关免疫反应性,包括C末端和中部胰高血糖素免疫反应性、N末端和C末端肠高血糖素免疫反应性、胰高血糖素样肽-1和胰高血糖素样肽-2免疫反应性。除了直肠黏膜和3个肿瘤中的少数散在细胞外,只有在对组织切片进行胰蛋白酶或枯草杆菌蛋白酶处理后才能获得C末端胰高血糖素免疫反应性。在直肠L细胞和类癌中均检测到肽YY和胰多肽/胰多肽前体样肽,正常细胞中肽YY占优势,肿瘤细胞中胰多肽/胰多肽前体样肽占优势。结论是,相同或密切相关的激素/前激素序列在直肠内分泌细胞和类癌肿瘤中合成并储存,尽管可能会出现定量表达、翻译后切割或抗体反应性的差异。概述了对组织切片进行蛋白酶处理以揭示未切割前体肽或固定剂变性肽的免疫反应性的实用性。