Di Meo Ashley, Rotondo Fabio, Kovacs Kalman, Cusimano Michael D, Syro Luis V, Di Ieva Antonio, Diamandis Eleftheros P, Yousef George M
*Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital †Department of Laboratory Medicine and Pathobiology §Department of Neurosurgery, St. Michael's Hospital, University of Toronto ‡Departments of Pathology and Laboratory Medicine, Division of Clinical Biochemistry, Mount Sinai Hospital and Clinical Biochemistry, University Health Network, Toronto, ON, Canada ∥Department of Neurosurgery, Hospital Pablo Tobon Uribe and Clinica Medellin, Medellin, Colombia.
Appl Immunohistochem Mol Morphol. 2015 Jul;23(6):433-7. doi: 10.1097/PAI.0000000000000108.
Human kallikrein 10 (hk10), a secreted serine protease, was reported to function as a tumor suppressor. hK10 immunoexpression has been demonstrated in lactrotrophs and corticotrophs of the nontumorous human adenohypophysis. In the present study, for the first time we report hK10 immunoexpression in various surgically removed corticotroph adenoma subtypes. Specimens were fixed in formalin and embedded in paraffin. Immunostaining was performed using the streptavidin-biotin-peroxidase complex method with an hK10-specific rabbit polyclonal antibody. Results showed that the endocrinologically active adrenocorticotropic hormone (ACTH)-producing pituitary tumors and the silent subtypes were immunopositve for hK10. Intensity of staining varied between the different subtypes. Intensity was lowest in the silent subtypes (silent corticotroph subtypes 1 and 2) compared with nontumorous human adenohypophysial corticotrophs, whereas the endocrinologically active subtypes (ACTH-secreting adenomas, corticotroph carcinomas, Crooke cell adenomas, Crooke cell carcinomas), showed the highest hK10 immunoexpression. Immunopositivity in the nuclei of the ACTH-secreting adenomas and carcinomas, as well as dual cytoplasmic and nuclear localization of hK10 in some of the secreting tumor types was an intriguing finding. Immunoexpression of hK10 in the ACTH-secreting tumors as well as in the Crooke cell tumors was significantly increased when compared with the nonfunctioning tumors and in the corticotrophs of nontumorous pituitaries.
人激肽释放酶10(hk10)是一种分泌型丝氨酸蛋白酶,据报道具有肿瘤抑制功能。hK10免疫表达已在非肿瘤性人腺垂体的催乳素细胞和促肾上腺皮质激素细胞中得到证实。在本研究中,我们首次报道了hK10在各种手术切除的促肾上腺皮质激素细胞腺瘤亚型中的免疫表达。标本用福尔马林固定并石蜡包埋。使用链霉亲和素-生物素-过氧化物酶复合物法和hK10特异性兔多克隆抗体进行免疫染色。结果显示,产生内分泌活性促肾上腺皮质激素(ACTH) 的垂体肿瘤和沉默亚型对hK10呈免疫阳性。不同亚型之间的染色强度有所不同。与非肿瘤性人腺垂体促肾上腺皮质激素细胞相比,沉默亚型(沉默促肾上腺皮质激素细胞亚型1和2)的染色强度最低,而内分泌活性亚型(分泌ACTH的腺瘤、促肾上腺皮质激素细胞瘤、克鲁克细胞腺瘤、克鲁克细胞癌)显示出最高的hK10免疫表达。分泌ACTH的腺瘤和癌细胞核中的免疫阳性,以及hK10在一些分泌性肿瘤类型中的细胞质和细胞核双重定位是一个有趣的发现。与无功能肿瘤和非肿瘤性垂体的促肾上腺皮质激素细胞相比,hK10在分泌ACTH的肿瘤以及克鲁克细胞肿瘤中的免疫表达显著增加。