Insulinoma-Associated Protein 1 (INSM1): Diagnostic, Prognostic, and Therapeutic Use in Small Cell Lung Cancer
Abstract
:1. Introduction
2. Methodology
3. INSM1 and SCLC Oncogenesis
4. INSM1 Diagnostic Use
4.1. Performance of INSM1 as a Diagnostic Biomarker
4.2. Immunohistochemistry
4.3. Immunocytochemistry
4.4. INSM1 Gene Expression and Diagnostic Use
4.5. INSM1 Diagnostic Use—Conclusions
Study | No. of SCLC Samples | Type of Sample | Preparation | INSM1 Positive Cutoff Value | INSM1 Sensitivity, % (Positive Cases/ Total Cases) | CGA/SYN/CD56 Sensitivity, % (Positive Cases/ Total Cases) | Combined Classic NE Markers Sensitivity, % (Positive Cases/ Total Cases) | INSM1 Specificity (SCLC vs. NSCLC *), % | INSM1 Expression on Other Lung NE Tumors: LCNEC/ Carcinoids (Typical and Atypical), % (Positive Cases/Total Cases) |
---|---|---|---|---|---|---|---|---|---|
Fujino 2015 [4] | 27 | Resections | FFPE section | Any nuclear staining in tumor cells | 100 (27/27) | 70 (19/27)/ 63 (17/27)/ n/a | n/a | 100 | n/a |
Fujino 2017 [38] | 19 | Resections | FFPE section | Any nuclear staining in tumor cells | 100 (19/19) | 74 (14/19)/ 58 (11/19)/ 68(13/19) | n/a | 100 | 100 (4/4)/ 100 (5/5) |
Rooper 2017 [37] | 39 | Resections (TMA) | FFPE section | Any nuclear staining in tumor cells | 95 (37/39) | 49 (19/39)/ 62 (24/39)/ 70 (21/30) | 74 (29/39) | 96 | 91 (21/23)/ 100 (48/48) ** |
Kriegsmann 2018 [35] | 144 | Resections (TMA) | FFPE section | ≥1% stained tumor cells in at least 1 of 2 cores per patient | 86 (124/144) | 74 (107/144)/ 85 (122/144)/ 92 (132/144) | 95 (137/144) | 99 | 42 (32/77)/ 79 (120/151) |
Doxtader 2018 [36] | 41 | Transbronchial FNA, CT-guided aspirates and a fluid cytology specimen | Cellient cell blocks | Any nuclear staining in tumor cells | 93 (38/41) | 35 (14/40)/ 93 (37/40)/ 100 (40/40) | 100 (40/40) | 100 | 100 (1/1)/ 90 (9/10) |
Rodriguez 2018 [34] | 32 | Aspirates (31) and bronchoalveolar lavage (1) | Cell blocks | Nuclear positivity in ≥1% tumor cells | 97 (31/32) | 63 (10/16)/ 78 (14/17)/ 96 (22/23) | n/a | 100 | n/a |
Abe 2019 *** [33] | 24 | Bronchial brushing | Cell blocks | 8.68% cutoff determined through ROC curve analysis | 98 (23/24) | Only SYN: 86 (21/24) | n/a | 100 | n/a |
Mukhopadhyay 2019 [23] | 64 | Small biopsies (32) and whole-tissue sections of resected tumor (32) | FFPE section | Any nuclear staining in tumor cells | 98 (63/64) | 83 (53/64)/ 100(64/64)/ 95 (61/64) | 100 (64/64) | 97 | 75 (18/24)/ 98 (63/64) |
Švajdler 2019 [31] | 112 | Endoscopic biopsies (112) | n/a | Any nuclear staining in tumor cells | 81 (81/100) | Only CD56: 84 (84/100) | n/a | n/a | n/a |
n/a—cytology sample (13) | Cell blocks (cytoblock) | 54 (7/13) | Only CD56: 100 (13/13) | ||||||
Nakra 2019 [32] | 60 | Aspirates (36) | Direct smears | Any nuclear staining in tumor cells | 91 (30/33) | n/a | n/a | 100 | n/a |
Small biopsies (37) | FFPE section | 97 (36/37) | 100 (18/18)/ 96 (27/28)/ 100 (6/6) | ||||||
Hou 2020 [29] | 11 | Aspirates | Direct smears | Nuclear positivity in ≥ 5% of tumor cells | 91 (10/11) | 73 (8/11)/ 82 (9/11)/ n/a | n/a | n/a | Only carcinoids: 90 (9/10) |
Narayanan 2020 [6] | 19 | Resections (TMA) | FFPE section | Any nuclear staining in tumor cells | 100 (19/19) | 80 (15/19)/ 100 (19/19)/ n/a | 100 (19/19) | n/a | 100 (9/9)/ 95 (83/87) |
Sakakibara 2020 [24] | 78 | Resections (whole slides and TMA) | FFPE section | Calculated H-score of 5 | 92 (72/78) | 48 (37/78)/ 55 (43/78)/ 81 (63/78) | 85 (66/78) | 95 | 68 (30/44)/ 95 (18/19) |
Staaf 2020 [28] | 24 | Resections (whole slides and TMA) and biopsies | FFPE section | Any nuclear staining in tumor cells | 92 (22/24) | 67 (16/24)/ 83 (20/24)/ 96(23/24) | n/a | 98 | 87 (20/23)/ 100 (7/7) |
At least 10% positive tumor cells | 75 (18/24) | 46 (11/24)/ 79 (19/24)/ 88 (21/24) | 88 (21/24) | 99 | 61 (14/23)/ 100 (7/7) |
5. INSM1 as a Prognostic Marker
6. Gene Therapy and Other Treatment Options Targeting INSM1 or Related Molecules
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Rocha, R.; Henrique, R. Insulinoma-Associated Protein 1 (INSM1): Diagnostic, Prognostic, and Therapeutic Use in Small Cell Lung Cancer. J. Mol. Pathol. 2022, 3, 140-167. https://doi.org/10.3390/jmp3030013
Rocha R, Henrique R. Insulinoma-Associated Protein 1 (INSM1): Diagnostic, Prognostic, and Therapeutic Use in Small Cell Lung Cancer. Journal of Molecular Pathology. 2022; 3(3):140-167. https://doi.org/10.3390/jmp3030013
Chicago/Turabian StyleRocha, Renato, and Rui Henrique. 2022. "Insulinoma-Associated Protein 1 (INSM1): Diagnostic, Prognostic, and Therapeutic Use in Small Cell Lung Cancer" Journal of Molecular Pathology 3, no. 3: 140-167. https://doi.org/10.3390/jmp3030013