胰腺神经内分泌肿瘤和实性假乳头状肿瘤中INSM1和SOX11的表达及意义

doi:10.19723/j.issn.1671-167X.2023.04.001

摘要/Abstract

摘要：

目的: 探讨胰岛素瘤相关蛋白1(insulinoma associated protein 1, INSM1)和SRY相关高迁移率族盒蛋白11(SRY -related high-mobility group box 11, SOX11)在胰腺神经内分泌肿瘤(pancreatic neuroendocrine tumor, PNET)和实性假乳头状肿瘤(solid pseudopapillary neoplasm, SPN)中的表达及意义。方法: 采用免疫组织化学方法在56例PNET、42例SPN、16例导管腺癌(ductal adenocarcinoma, DACC) 和8例腺泡细胞癌(acinar cell carcinoma, ACC)中检测INSM1、SOX11、Syn、CgA、CD56、β-catenin和CD99, 比较INSM1和SOX11的组合与传统标记物(Syn、CgA、CD56、β-catenin和CD99)在诊断和鉴别诊断PNET和SPN中的应用价值。结果: (1) 56例PNET中, INSM1表达于肿瘤细胞及胰岛细胞核, 其在肿瘤组织中的阳性表达率为91.07% (51/56);42例SPN、16例DACC和8例ACC均未见INSM1的阳性信号。INSM1在PNET中的阳性表达率与SPN、DACC和ACC相比, 差异均有统计学意义(P < 0.001)。(2)42例SPN中, SOX11的阳性信号位于肿瘤细胞核, 其阳性表达率为92. 86% (39/42);56例PNET中, SOX11的阳性表达率为8. 93% (5/56), 其阳性信号位于3例G₁，型和2例G₃型PNET; 16例DACC、8例ACC及肿瘤旁的正常胰腺组织均未见SOX11阳性信号; SOX11在SPN中的阳性表达率与PNET、DACC和ACC相比, 差异均有统计学意义(P < 0.001)。(3) INSM1(+)/SOX11(-)免疫表型对PNET的敏感度为85.71%, 与CD56(57. 14%)相比差异有统计学意义(P = 0.001), 与Syn(80.36%)和CgA(71. 43%)相比差异无统计学意义(P > 0. 05);其特异度为100. 00%，与Syn(42. 86%)和CD56(47. 62%)相比差异有统计学意义(P < 0.001), 与CgA(92.86%)相比差异无统计学意义(P > 0.05)。INSM1(-)/SOX11(+)免疫表型对SPN的敏感度为92. 86%, 与β-catenin(90. 48%)和CD99(85. 71%)相比差异无统计学意义(P > 0.05);其特异度为96.43%, 与CD99(48. 21%)相比差异有统计学意义(P < 0.001), 与β-catenin(100. 00%)相比差异无统计学意义(P > 0.05)。(4)在PNET和SPN中, INSM1和SOX11的表达情况与临床病理参数(患者年龄、性别、肿瘤大小、部位、分级及转移)无关(P均> 0.05)。结论: 在PNET和SPN中, INSM1和SOX11分别呈阳性的表达模式有助于区分两种肿瘤, 两者组合在敏感度和特异度方面优于-.些传统的免疫组织化学标记物。

关键词: 生物标记，肿瘤, 神经内分泌瘤, 胰腺肿瘤, 胰岛素瘤相关蛋白1, SRY相关高迁移率族盒11

Abstract:

Objective: To investigate the expression and significance of insulinoma associated protein 1 (INSM1) and SRY-related high-mobility group box 11 (SOX11) in pancreatic neuroendocrine tumor (PNET) and solid pseudopapillary neoplasm (SPN). Methods: To detect the expression of INSM1, SOX11, Syn, CgA, CD56, β-catenin, and CD99 in 56 cases of PNET, 42 cases of SPN, 16 cases of ductal adenocarcinoma (DACC) and 8 cases of acinar cell carcinoma (ACC) by immunohistochemistry. The application value of combination of INSM1 and SOX11 was compared with conventional markers (Syn, CgA, CD56, β-catenin, and CD99) in diagnosis and differential diagnosis of PNET and SPN. Results: (1) In the 56 cases of PNET, the positive signals of INSM1 were located in the tumor and islet nucleus, the positive expression rate in the tumor tissues was 91.07% (51/56), whereas the signal was absent in 42 cases of SPN, 16 cases of DACC and 8 cases of ACC, and there were significant statistical difference between PNET with SPN, DACC, and ACC respectively (P < 0.001). (2) The positive signals of SOX11 were located in the tumor nucleus, with the positive expression rate was 92.86% (39/42) in SPN, however, the positive expression rate of SOX11 was 8.93% (5/56) in PNET, which included 3 cases of G₁ and 2 cases of G₃ types of PNET, the SOX11 positive signal was absent in 16 cases of DACC, 8 cases of ACC and peritumoral nomal pancreatic tissue, and the differences were statistically significant of positive rate between SPN with PNET, DACC and ACC, respectively (P < 0.001). (3) The sensitivity of INSM1(+)/SOX11(-) immunophenotype for PNET was 85.71%, vs. CD56 (57.14%), the difference was statistically significant (P=0.001); vs. Syn (80.36%) and CgA (71.43%), the difference was no statistically significant (P>0.05). The specificity of INSM1(+)/SOX11(-) for PNET was 100.00%, vs. Syn (42.86%) and CD56 (47.62%), the difference was statistically significant (P < 0.001); vs. CgA (92.86%), the difference was no statistically significant (P>0.05). The sensitivity of INSM1(-)/SOX11(+) immunophenotype for SPN was 92.86%, vs. β-catenin (90.48%) and CD99 (85.71%), the difference was no statistically significant (P>0.05). The specificity of INSM1(-)/SOX11(+) for SPN was 96.43%, vs. CD99 (48.21%), the difference was statistically significant (P < 0.001); vs. β-catenin (100.00%), the difference was no statistically significant (P>0.05). (4) The positive expression of INSM1 and SOX11 in PNET and SOX11 were not correlated with clinicopathological parameters (age, gender, tumor size, location, grade, and metastasis) (P>0.05). Conclusion: The positive expression patterns of INSM1 and SOX11 in PNET and SPN respectively are conductive to distinguish the both tumors. The combination of both take precedence over some corresponding conventional immunohistochemical markers in terms of sensitivity and specificity.

Key words: Biomarkers, tumor, Neuroendocrine tumors, Pancreatic neoplasms, Insulinoma associated protein 1, SRY-related high-mobility group box 11

中图分类号:

R735.9

曹钟,岑红兵,赵建红,梅俊,秦灵芝,廖伟,敖启林. 胰腺神经内分泌肿瘤和实性假乳头状肿瘤中INSM1和SOX11的表达及意义[J]. 北京大学学报（医学版）, 2023, 55(4): 575-581.

Zhong CAO,Hong-bing CEN,Jian-hong ZHAO,Jun MEI,Ling-zhi QIN,Wei LIAO,Qi-lin AO. Expression and significance of INSM1 and SOX11 in pancreatic neuroendocrine tumor and solid pseudopapillary neoplasm[J]. Journal of Peking University (Health Sciences), 2023, 55(4): 575-581.

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参考文献 18

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Tumor types	n	INSM1 (+), n (%)	SOX11 (+), n (%)	Syn (+), n (%)	CgA (+), n (%)	CD56 (+), n (%)	β-catenin (+), n (%)	CD99 (+), n (%)
PNET	56	51 (91.07)	5 (8.93)	45 (80.36)	40 (71.43)	32 (57.14)	0 (0)	29 (51.79)
SPN	42	0 (0)	39 (92.86)	24 (57.14)	3 (7.14)	22 (52.38)	38 (90.48)	36 (85.71)
DACC	16	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
ACC	8	0 (0)	0 (0)	1 (12.50)	1 (12.50)	0 (0)	0 (0)	0 (0)

Items	INSM1 (+)		R value	P value
Items	n	%	R value	P value
Male	31/32	96.88	0.235	0.081
Female	20/24	83.33
Age ≥46 years	33/36	91.67	0.028	0.838
Age <46 years	18/20	90.00
Size ≥6.3 cm	31/33	93.94	0.120	0.376
Size <6.3 cm	20/23	86.96
Pancreatic tail	35/37	94.59	0.172	0.204
Non-pancreatic tail	16/19	84.21
G₁ type	23/24	95.83	0.145	0.288
G₂+G₃ type	28/32	87.50
Metastasis	5/6	83.33	0.094	0.491
Non-metastasis	46/50	92.00

Items	SOX11 (+)		R value	P value
Items	n	%	R value	P value
Male	12/13	92.31	0.014	0.928
Female	27/29	93.10
Age ≥29 years	16/16	100.00	0.218	0.166
Age <29 years	23/26	88.46
Size ≥7.3 cm	12/14	85.71	0.196	0.213
Size <7.3 cm	27/28	96.43
Pancreatic tail	24/25	96.00	0.148	0.350
Non-pancreatic tail	15/17	88.24
Metastasis	10/11	90.91	0.045	0.777
Non-metastasis	29/31	93.55

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