Siiskonen Hanna, Poukka Mari, Bykachev Andrey, Tyynelä-Korhonen Kristiina, Sironen Reijo, Pasonen-Seppänen Sanna, Harvima Ilkka T
aDepartment of Dermatology bInstitute of Biomedicine/Anatomy cInstitute of Clinical Medicine/Clinical Pathology dCancer Center of Eastern Finland, University of Eastern Finland eCancer Center fDepartment of Clinical Pathology gDepartment of Dermatology, Kuopio University Hospital, Kuopio, Finland.
Melanoma Res. 2015 Dec;25(6):479-85. doi: 10.1097/CMR.0000000000000192.
The role of mast cells in cutaneous melanoma remains unclear. Tryptase and chymase are serine proteinases and major proteins in mast cell secretory granules. Therefore, this study aimed to investigate the presence of tryptase and chymase mast cells in benign and malignant cutaneous melanocytic lesions and in lymph node metastases of melanomas. The presence of positively stained mast cells was correlated with clinicopathological characteristics in invasive melanomas. Paraffin-embedded sections of 28 benign (13 intradermal, 10 compound, and five junctional nevi) and 26 dysplastic nevi, 15 in-situ melanomas, 36 superficially (pT1, Breslow's thickness<1 mm), and 49 deeply (pT4, Breslow's thickness>4 mm) invasive melanomas and 30 lymph node metastases were immunohistochemically stained for mast cell tryptase and chymase, and immunopositive cells were counted using the hotspot counting method. The mean count of tryptase and chymase mast cells was lower in invasive melanomas compared with in-situ melanomas and dysplastic and benign nevi. In deeply invasive melanomas, the difference was statistically significant compared with dysplastic nevi (P=0.003 for tryptase and P=0.009 for chymase) and in-situ melanomas (0.043 for tryptase). Low numbers of tryptase mast cells were associated with poor overall survival (P=0.031) in deeply invasive melanomas and with a more advanced stage (T1b, P=0.008) in superficially invasive melanomas. Low numbers of chymase mast cells were associated with microsatellites (P=0.017) in deeply invasive melanomas. The results suggest that these serine proteinases of mast cells may be protective in the pathogenesis of melanoma.
肥大细胞在皮肤黑色素瘤中的作用仍不清楚。类胰蛋白酶和糜蛋白酶是丝氨酸蛋白酶，也是肥大细胞分泌颗粒中的主要蛋白质。因此，本研究旨在调查类胰蛋白酶和糜蛋白酶阳性肥大细胞在良性和恶性皮肤黑素细胞病变以及黑色素瘤淋巴结转移中的存在情况。在侵袭性黑色素瘤中，阳性染色肥大细胞的存在与临床病理特征相关。对28例良性病变（13例皮内痣、10例复合痣和5例交界痣）、26例发育异常痣、15例原位黑色素瘤、36例浅表性（pT1， Breslow厚度<1mm）和49例深部（pT4， Breslow厚度>4mm）侵袭性黑色素瘤以及30例淋巴结转移的石蜡包埋切片进行免疫组化染色，检测肥大细胞类胰蛋白酶和糜蛋白酶，并采用热点计数法对免疫阳性细胞进行计数。与原位黑色素瘤、发育异常痣和良性痣相比，侵袭性黑色素瘤中类胰蛋白酶和糜蛋白酶阳性肥大细胞的平均计数较低。在深部侵袭性黑色素瘤中，与发育异常痣相比（类胰蛋白酶P = 0.003，糜蛋白酶P = 0.009）以及与原位黑色素瘤相比（类胰蛋白酶P = 0.043），差异具有统计学意义。在深部侵袭性黑色素瘤中，类胰蛋白酶阳性肥大细胞数量少与总生存率低相关（P = 0.031），在浅表性侵袭性黑色素瘤中与分期更晚相关（T1b，P = 0.008）。在深部侵袭性黑色素瘤中，糜蛋白酶阳性肥大细胞数量少与微卫星相关（P = 0.017）。结果表明，肥大细胞的这些丝氨酸蛋白酶可能在黑色素瘤的发病机制中具有保护作用。
