Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (4): 575-581. doi: 10.19723/j.issn.1671-167X.2023.04.001

    Next Articles

Expression and significance of INSM1 and SOX11 in pancreatic neuroendocrine tumor and solid pseudopapillary neoplasm

Zhong CAO1,Hong-bing CEN1,Jian-hong ZHAO1,Jun MEI2,Ling-zhi QIN3,Wei LIAO4,*(),Qi-lin AO3   

  1. 1. Department of Pathology, Huanggang Central Hospital, Huanggang 438000, Hubei, China
    2. Department of Thyroid and Breast Surgery, Huanggang Central Hospital, Huanggang 438000, Hubei, China
    3. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
    4. Department of Respiratory and Critical Care Medicine, Fifth Hospital in Wuhan, 430050, China
  • Received:2020-07-14 Online:2023-08-18 Published:2023-08-03
  • Contact: Wei LIAO E-mail:lyminister@163.com

RICH HTML

   

PDF (PC)

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

CLC Number: 

  • R735.9

Figure 1

Expression patterns of INSM1 (En Vision ×200) A, in nomal pancreatic islets; B, in G1 type of PNET; C, in large cell G3 type of PNET; D, in small cell G3type of PNET.PNET, pancreatic neuroendocrine tumor; INSM1; insulinoma associated protein 1."

Table 1

Expression of INSM1, SOX11 and convention immunohistochemical markers in four kinds of pancreatic solid tumors."

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)

Figure 2

Expression patterns of SOX11 (En Vision ×200) A, in pseudopapillary region of SPN; B, in solid region of SPN; C, in PNET.SOX11, SRY-related high-mobility group box 11; PNET, pancreatic neuroendocrine tumor; SPN, solid pseudopapillary neoplasm."

Table 2

Expression of combination INSM1 and SOX11 in PNET and SPN"

Tumor types n INSM1(+)/SOX11(+) INSM1(+)/SOX11(-) INSM1(-)/SOX11(+) INSM1(-)/SOX11(-)
PNET 56 3 48 2 3
SPN 42 0 0 39 3

Table 3

Sensitivity and specificity of INSM1(+)/SOX11(-) phenotype in PNET"

Markers Sensitivity/% Specificity/%
Syn 80.36 42.86
CgA 71.43 92.86
CD56 57.14 47.62
INSM1(+)/SOX11(-) 85.71 100.00

Table 4

Sensitivity and specificity of INSM1(-)/SOX11(+) phenotype in SPN"

Markers Sensitivity/% Specificity/%
β-catenin 90.48 100.00
CD99 85.71 48.21
INSM1(-)/SOX11(+) 92.86 96.43

Table 5

Correlation between the expression of INSM1 in PNET and clinicopathological parameters"

Items INSM1 (+) R value P value
n %
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

Table 6

Correlation between the expression of SOX11 in SPN and clinicopathological parameters"

Items SOX11 (+) R value P value
n %
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
1 Klimstra DS , Hruban RH , Klöppel G , et al. WHO classification of tumours of the digestive system[M]. Lyon: IARC, 2010: 327- 330.
2 McHugh KE , Mukhopadhyay S , Doxtader EE , et al. INSM1 is a highly specific marker of neuroendocrine differentiation in primary neoplasms of the gastrointestinal tract, appendix, and pancreas[J]. Am J Clin Pathol, 2020, 153 (6): 811- 820.
doi: 10.1093/ajcp/aqaa014
3 Zhang T , Liu WD , Saunee NA , et al. Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest[J]. J Biol Chem, 2009, 284 (9): 5574- 5581.
doi: 10.1074/jbc.M808843200
4 Wang H , Chen Y , Fernandez-Del Castillo C , et al. Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: A critical look at notch signaling pathway[J]. Mod Pathol, 2013, 26 (1): 139- 147.
doi: 10.1038/modpathol.2012.143
5 Fujino K , Motooka Y , Hassan WA , et al. Insulinoma-associated protein 1 is a crucial regulator of neuroendocrine differentiation in lung cancer[J]. Am J Pathol, 2015, 185 (12): 3164- 3177.
doi: 10.1016/j.ajpath.2015.08.018
6 Rooper LM , Bishop JA , Westra WH . INSM1 is a sensitive and specific marker of neuro-endocrine differentiation in head and neck tumor[J]. Am J Surg Pathol, 2018, 42 (5): 665- 671.
doi: 10.1097/PAS.0000000000001037
7 Sakakibara R , Kobayashi M , Takahashi N , et al. Insulinoma-associated protein 1(INSM1) is a better marker for the diagnosis and prognosis estimation of small cell lung carcinoma than neuroendocrine phenotype markers such as chromogranin A, synaptophysin, and CD56[J]. Am J Surg Pathol, 2020, 44 (6): 757- 764.
doi: 10.1097/PAS.0000000000001444
8 Kriegsmann K , Zgorzelski C , Kazdal D , et al. Insulinoma-asso-ciated protein 1 (INSM1) in thoracic tumors is less sensitive but more specific compared with synaptophysin, chromogranin A, and CD56[J]. Appl Immunohistochem Mol Morphol, 2020, 28 (3): 237- 242.
doi: 10.1097/PAI.0000000000000715
9 Kim IE Jr , Amin A , Wang LJ , et al. Insulinoma-associated protein 1 (INSM1) expression in small cell neuroendocrine carcinoma of the urinary tract[J]. Appl Immunohistochem Mol Morphol, 2020, 28 (9): 687- 693.
doi: 10.1097/PAI.0000000000000824
10 Takase Y , Naito Y , Okabe Y , et al. Insulinoma-associated protein 1 expression in pancreatic neuroendocrine tumours in endoscopic ultrasound-guided fine-needle aspiration cytology: An analysis of 14 patients[J]. Cytopathology, 2019, 30 (2): 194- 200.
doi: 10.1111/cyt.12640
11 Tanigawa M , Nakayama M , Taira T , et al. Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor[J]. Med Mol Morphol, 2018, 51 (1): 32- 40.
doi: 10.1007/s00795-017-0167-6
12 Kim D , Viswanathan K , Goyal A , et al. Insulinoma-associated protein 1 (INSM1) is robust marker for identifying and grading pancreatic neuroendocrine tumors[J]. Cancer Cytopathol, 2020, 128 (4): 269- 277.
doi: 10.1002/cncy.22242
13 Li P , Hu Y , Yi J , et al. Identification of potential biomarkers to differentially diagnose solid pseudopapillary tumors and pancreatic malignancies via a gene regulatory network[J]. J Transl Med, 2015, 13, 361.
doi: 10.1186/s12967-015-0718-3
14 Harrison G , Hemmerich A , Guy C , et al. Overexpression of SOX11 and TFE3 in solid-pseudopapillary neoplasms of the pancreas[J]. Am J Clin Pathol, 2017, 149 (1): 67- 75.
15 Foo WC , Harrison G , Zhang X . Immunocytochemistry for SOX-11 and TFE3 as diagnostic markers for solid pseudopapillary neoplasms of the pancreas in FNA biopsies[J]. Cancer Cytopathol, 2017, 125 (11): 831- 837.
doi: 10.1002/cncy.21931
16 Moradi A , Ghasemi F , Anvari K , et al. The cross-regulation between SOX15 and Wnt signaling pathway[J]. J Cell Physiol, 2017, 232 (12): 3221- 3225.
doi: 10.1002/jcp.25802
17 Bernard P , Harley VR . Acquisition of SOX transcription factor specificity through protein-protein interaction, modulation of Wnt signaling and post-translational modification[J]. Int J Biochem Cell Biol, 2010, 42 (3): 400- 410.
doi: 10.1016/j.biocel.2009.10.017
18 Zhao T , Yang H , Tian Y , et al. SOX7 is associated with the suppression of human glioma by HMG-box dependent regulation of Wnt/β-catenin signaling[J]. Cancer Lett, 2016, 375 (1): 100- 107.
doi: 10.1016/j.canlet.2016.02.044
No related articles found!
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Journal of Peking University(Health Sciences), 2009, 41(2): 158 -161 .
[2] . [J]. Journal of Peking University(Health Sciences), 2001, 33(1): 89 -91 .
[3] . [J]. Journal of Peking University(Health Sciences), 2001, 33(4): 383 -385 .
[4] . [J]. Journal of Peking University(Health Sciences), 2002, 34(1): 86 -87 .
[5] . [J]. Journal of Peking University(Health Sciences), 2008, 40(2): 214 -218 .
[6] . [J]. Journal of Peking University(Health Sciences), 2011, 43(1): 29 -33 .
[7] . [J]. Journal of Peking University(Health Sciences), 2009, 41(6): 721 -722 .
[8] . [J]. Journal of Peking University(Health Sciences), 2010, 42(1): 94 -97 .
[9] . [J]. Journal of Peking University(Health Sciences), 2009, 41(5): 565 -570 .
[10] . [J]. Journal of Peking University(Health Sciences), 2009, 41(3): 255 -258 .
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd