This document discusses the utility of INSM1 immunohistochemistry in diagnosing neuroendocrine tumors. It finds that INSM1 outperforms traditional markers like synaptophysin and chromogranin in identifying thoracic neuroendocrine tumors, including high-grade neuroendocrine carcinomas. INSM1 staining is highly sensitive and specific, and easier to interpret than other markers due to its crisp nuclear pattern. The study concludes that INSM1 can be used as a standalone first-line marker for neuroendocrine differentiation.

1. INSM1
Aplicaciones y ventajas en el diagnóstico de tumores
neuroendócrinos.
Dra. Mónica García Falcone
Actualización de Nuevos Marcadores de IHC

2. INSM1
• Insulinoma associated protein 1
• Es un factor de transcripción nuclear
– Recluta ciclinda D1 y histone deacetylases… actividad represora
• Marcador NUCLEAR PAN-NEUROENDOCRINO
• Expresión en amplio espectro de tumores NE,
de tejidos NE y tejidos fetales.
• Potencial BIOMARCADOR NE para desarrollo
terapia específica para SCLC.
Mol Cancer Res. 2019 Aug;17(8):1597-1604

3. Marcadores NE tradicionales:
Sinpatofisina, Cromogranina A, CD56,
CD57, PGP9.5, enolase neurono-específica

4. Algorithmic approach to neuroendocrine tumors in targeted biopsies: Practical
applications of immunohistochemical markers
Cancer Cytopathology, Volume: 124, Issue: 12, Pages: 871-884, First published: 2016, DOI: (10.1002/cncy.21765)
GATA3

5. Características de marcadores
tradicionales
• Cromogranina A: + especifico
– expresión puede ser focal/negativa según ≠ tx
• Sinaptofisina: + sensible
– pero da + Tx no NE, por ej. tx solido pseudopapilar
y carcinoma adrenal
• Después de confirmar positividad para
marcadores NE, se recomienda Citokeratinas
– Si da negativo: considerar paraganglioma … GATA3
Morfológicamente son diferentes, pero los tumores NEUROEPITELIALES
(meduloblastoma, retinoblasotma, neuroblastoma olfatorio) también expresan

6. Determinación del sitio primario
• Clasificación WHO depende del SITIO 1rio y
grado
• Como saber de donde viene un WDNET?
– TTF1: head and neck (carcinoma medular) o
tórax(carcinoide pulmonar).
– Calcitonin: medular y carcinoide pulmonar.
• Los NE pobremente diferenciados suelen dar
TTF-1
– CK20: Merkel.

7. Ventajas INSM1
• MUY ESPECEFICIO
– No se expresa en TX no NE / neuroepiteliales
– Excepción: es Negativo en adenoma Paratiroideo
• SENSIBLE
– tx NE, neuroepitelial y paraganglioma
– 95% en NE de alto grado
• NUCLEAR
– Fácil interpretar y cuantificar (por ej. teratoma, tx
mixtos)

8. • Background: Smaller panels are needed, not larger ones, when it comes to
the accurate subclassification of pulmonary tumors.
• Métodos: In this study, we performed INSM1 immunohistochemistry on
thoracic neuroendocrine and non-neuroendocrine tumors to determine if
this single marker could replace the traditional panel of synaptophysin,
chromogranin, and CD56 staining to discern the presence of
neuroendocrine differentiation.
Am J Surg Pathol 2017;00:000–00

9. • Overall, INSM1 demonstrated excellent performance for the diagnosis of thoracic
neuroendocrine tumors.
– Indeed, it outperformed all of the other neuroendocrine markers individually and in combination for
high-grade neuroendocrine carcinomas.
– It also demonstrated equivalent performance for low-grade to intermediate-grade neuroendocrine
neoplasms, with INSM1 staining being invariably present in all of the typical carcinoids, atypical
carcinoids, and mediastinal paragangliomas.
• INSM1 staining was found to be easy to interpret. Not only did INSM1
staining match the intensity and distribution of staining of the traditional
neuroendocrine markers, but its crisp nuclear signals were easier to discern
as positive in cases with weak or focal reactivity.

10. Conclusiones
• In contrast, INSM1 demonstrates 94.6% overall
sensitivity for thoracic neuroendocrine tumors.
• Our findings support the use of INSM1 staining
as a standalone first-line marker of
neuroendocrine differentiation.
• The significance of limited INSM1 expression in
non-neuroendocrine carcinomas is unclear,
although it does not seem likely to pose a
diagnostic problem.
• Focal staining was noted in only 3.3% of ACAs and
4.2% of SqCCs.

11. Bibliografía
1. Chen C, Notkins AL, Lan MS. Insulinoma-Associated-1: From
Neuroendocrine Tumor Marker to Cancer Therapeutics. Mol Cancer Res.
2019;17(8):1597-1604.
2. Rosenbaum JN, et al. INSM1. A Novel Immunohistochemical and Molecular
Marker for Neuroendocrine and Neuroepithelial Neoplasms. Am J Clin
Pathol. 2015;144:579-591.
3. Kai Duan, Ozgur Mete. Algorithmic Approach to Neuroendocrine Tumors in
Targeted Biopsies: Practical Applications of Immunohistochemical Markers.
Cancer Cytopathol. 2016;124(12):871-884.
4. Rooper LM, Bishop JB, Westra WH. INSM1 Is a Sensitive and Specific Marker
of Neuroendocrine Differentiation in Head and Neck Tumors. Am J Surg
Pathol. 2018;42(5):665-671.
5. Rooper LM, et al. INSM1 Demonstrates Superior Performance to the
Individual and Combined Use of Synaptophysin, Chromogranin and CD56
for Diagnosing Neuroendocrine Tumors of the Thoracic Cavity. Am J Surg
Pathol 2017;00:000–00