INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Maleki, Zahra; Nadella, Akash; Nadella, Mohnish; Patel, Gopi; Patel, Salil G.; Kholová, Ivana

doi:10.3390/diagnostics11122172

Cited by 29 publications

(28 citation statements)

References 79 publications

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“…Multiple immune-histochemical studies demonstrated that the detection of INSM1 expression is a super sensitive and specific diagnostic biomarker in NETs as compared with conventional NE markers (CGA, SYP, and CD56) [ 54 , 55 ]. Functional studies of INSM1 in NETs revealed that INSM1 exhibited regulatory roles in the cellular signaling axis critical for cell growth and oncogenesis including NB [ 3 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, INSM1 has emerged in clinical practice as a sensitive and specific diagnostic biomarker in NE tumors (NETs). This novel biomarker provides pathologists a useful tool to distinguish NETs from non-NETs, and it represents a more sensitive NE marker as compared to the traditional markers, such as synaptophysin, chromogranin A, and CD56 [ 54 ]. INSM-1 nuclear expression in cytology specimens successfully shows that it is a robust NE marker.…”

Section: Introductionmentioning

confidence: 99%

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Interplay: The Essential Role between INSM1 and N-Myc in Aggressive Neuroblastoma

Chen

Lan

2022

Biology

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An aggressive form of neuroblastoma (NB), a malignant childhood cancer derived from granule neuron precursors and sympathoadrenal lineage, frequently comprises MYCN amplification/elevated N-Myc expression, which contributes to the development of neural crest-derived embryonal malignancy. N-Myc is an oncogenic driver in NB. Persistent N-Myc expression during the maturation of SA precursor cells can cause blockage of the apoptosis and induce abnormal proliferation, resulting in NB development. An insulinoma-associated-1 (INSM1) zinc-finger transcription factor has emerged as an NB biomarker that plays a critical role in facilitating tumor cell growth and transformation. INSM1 plays an essential role in sympathoadrenal cell differentiation. N-Myc activates endogenous INSM1 through an E2-box of the INSM1 proximal promoter, whereas INSM1 enhances N-Myc stability via RAC-α-serine/threonine protein kinase (AKT) phosphorylation in NB. The ectopic expression of INSM1 stimulates NB tumor growth in contrast to the knockdown of INSM1 that inhibits NB cell proliferation. The clinical pathological result and bioinformatics analysis show that INSM1 is a strong diagnostic and a prognostic biomarker for the evaluation of NB progression. The INSM1/N-Myc expression shows high clinical relevance in NB. Therefore, targeting the INSM1/N-Myc-associated signaling axis should be a feasible approach to identifying new drugs for the suppression of NB tumor growth.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interplay: The Essential Role between INSM1 and N-Myc in Aggressive Neuroblastoma

Chen

Lan

2022

Biology

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“…However, use of morphology alone is challenging in tumor specimens from patients who have been treated with agents such as ADT or ARSIs that may alter cellular morphology and give a false impression of the phenotype of a tumor. Another approach is to use immunohistochemistry for canonical NEPC markers, including CHGA, SYP, NSE, CD56 (NCAM1), or INSM1 that are highly expressed in de novo NEPC (114)(115)(116). However, many t-NEPC tumors do not have high expression of these genes, presumably because they are not as far along the continuum of NEPC differentiation as a de novo NEPC tumor (26).…”

Section: Identifying Nepc Tumorsmentioning

confidence: 99%

The Role of Epigenetic Change in Therapy-Induced Neuroendocrine Prostate Cancer Lineage Plasticity

et al. 2022

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The androgen receptor (AR) signaling pathway is critical for growth and differentiation of prostate cancer cells. For that reason, androgen deprivation therapy with medical or surgical castration is the principal treatment for metastatic prostate cancer. More recently, new potent AR signaling inhibitors (ARSIs) have been developed. These drugs improve survival for men with metastatic castration-resistant prostate cancer (CRPC), the lethal form of the disease. However, ARSI resistance is nearly universal. One recently appreciated resistance mechanism is lineage plasticity or switch from an AR-driven, luminal differentiation program to an alternate differentiation program. Importantly, lineage plasticity appears to be increasing in incidence in the era of new ARSIs, strongly implicating AR suppression in this process. Lineage plasticity and shift from AR-driven tumors occur on a continuum, ranging from AR-expressing tumors with low AR activity to AR-null tumors that have activation of alternate differentiation programs versus the canonical luminal program found in AR-driven tumors. In many cases, AR loss coincides with the activation of a neuronal program, most commonly exemplified as therapy-induced neuroendocrine prostate cancer (t-NEPC). While genetic events clearly contribute to prostate cancer lineage plasticity, it is also clear that epigenetic events—including chromatin modifications and DNA methylation—play a major role. Many epigenetic factors are now targetable with drugs, establishing the importance of clarifying critical epigenetic factors that promote lineage plasticity. Furthermore, epigenetic marks are readily measurable, demonstrating the importance of clarifying which measurements will help to identify tumors that have undergone or are at risk of undergoing lineage plasticity. In this review, we discuss the role of AR pathway loss and activation of a neuronal differentiation program as key contributors to t-NEPC lineage plasticity. We also discuss new epigenetic therapeutic strategies to reverse lineage plasticity, including those that have recently entered clinical trials.

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“…This kind of study has essential output on patient management and quality of treatment. Another marker covered in the Special Issue is a new neuroendocrine biomarker insulinoma-associated protein 1 (INSM1) [ 10 ]. The nuclear expression of INSM1 is practical in all kinds of cytological preparations.…”

mentioning

confidence: 99%

“…The nuclear expression of INSM1 is practical in all kinds of cytological preparations. The review by Maleki et al concluded that INSM1 is a reliable sensitive and specific neuroendocrine marker in various localizations [ 10 ].…”

mentioning

confidence: 99%

Cyto-Histopathological Correlations in Pathology Diagnostics

Kholová

2022

Diagnostics

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INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Cited by 29 publications

References 79 publications

Interplay: The Essential Role between INSM1 and N-Myc in Aggressive Neuroblastoma

Interplay: The Essential Role between INSM1 and N-Myc in Aggressive Neuroblastoma

The Role of Epigenetic Change in Therapy-Induced Neuroendocrine Prostate Cancer Lineage Plasticity

Cyto-Histopathological Correlations in Pathology Diagnostics

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