Substance P and Its Receptor Are Overexpressed in All Types of Thyroid Cancer

Substance P and neurokinin-1 receptor were found in all thyroid cancer types with higher expression than normal tissue, suggesting NK-1R as a potential drug target.

Isorna, Inmaculada et al.·European journal of histochemistry : EJH·2020·Preliminary EvidenceImmunohistochemistry (observational)
RPEP-04878Immunohistochemistry (observational)Preliminary Evidence2020RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Immunohistochemistry (observational)
Evidence
Preliminary Evidence
Sample
Human thyroid cancer samples (papillary, follicular, medullary, anaplastic) and normal thyroid tissue
Participants
Human thyroid cancer samples (papillary, follicular, medullary, anaplastic) and normal thyroid tissue

What This Study Found

Both Substance P (SP) and the neurokinin-1 receptor (NK-1R) were expressed in all thyroid tissue, normal and cancerous. But the pattern differed significantly:

In healthy thyroid: SP was found in follicular cell nuclei and colloid. NK-1R was in follicular cell cytoplasm and stroma.

In thyroid cancer: SP expanded to follicular cell cytoplasm (not just nucleus), stroma, and colloid. NK-1R appeared in colloid (not present in normal tissue).

Using the Allred scoring system (a semi-quantitative measure of protein expression), both SP and NK-1R had higher total scores in cancer compared to normal thyroid. SP in nuclei, cytoplasm, and stroma was more intense/abundant in cancer. NK-1R in cytoplasm and colloid was higher in cancer.

Interestingly, SP in colloid was actually lower in cancer than in normal thyroid, and NK-1R in stroma was higher in normal tissue than cancer.

All four thyroid cancer types (papillary, follicular, medullary, anaplastic) and metastases showed the elevated pattern.

Key Numbers

SP and NK-1R in all samples; higher Allred scores in cancer; all 4 cancer types + metastases affected; SP expanded to cytoplasm in cancer

How They Did This

Immunohistochemistry study of human thyroid tissue samples: papillary, follicular, medullary, and anaplastic thyroid cancer, metastases, and healthy thyroid. SP and NK-1R protein expression scored using the Allred Unit Scoring System (combines intensity and proportion).

Why This Research Matters

Thyroid cancer incidence has tripled over 30 years. While most cases have good prognosis with surgery, anaplastic thyroid cancer is nearly universally fatal. Finding that NK-1R is overexpressed in all thyroid cancer types, including anaplastic, opens a potential therapeutic target. NK-1R antagonists (originally developed for nausea and depression) have shown anticancer effects in preclinical studies.

The Bigger Picture

Thyroid cancer incidence has tripled over 30 years. While most types are treatable, anaplastic thyroid cancer is nearly always fatal. NK-1R overexpression across all types, including anaplastic, suggests a common drug target for this diverse cancer family.

What This Study Doesn't Tell Us

Immunohistochemistry shows presence but not function. Higher expression does not prove SP/NK-1R drives cancer growth. No functional studies (NK-1R antagonist testing on thyroid cancer cells). Sample sizes per cancer type not specified in the abstract. Semi-quantitative scoring is subjective. The study did not measure SP/NK-1R correlation with cancer aggressiveness or patient outcomes.

Questions This Raises

  • ?Would NK-1R antagonists like aprepitant have anti-tumor effects in thyroid cancer?
  • ?Does SP/NK-1R signaling drive thyroid cancer growth or is it a bystander?
  • ?Could NK-1R expression serve as a diagnostic or prognostic marker?

Trust & Context

Key Stat:
All 4 cancer types papillary, follicular, medullary, and anaplastic thyroid cancers all overexpress the NK-1 receptor drug target
Evidence Grade:
Preliminary evidence from immunohistochemistry. Expression is demonstrated but functional role and therapeutic potential are not tested.
Study Age:
Published in 2020. NK-1R targeting in cancer is being explored across multiple tumor types.
Original Title:
The substance P and neurokinin-1 receptor system in human thyroid cancer: an immunohistochemical study.
Published In:
European journal of histochemistry : EJH, 64(2) (2020)
Database ID:
RPEP-04878

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

What is the NK-1 receptor and why target it in cancer?

NK-1R is activated by Substance P and promotes cell growth and survival. When overexpressed in cancer, it may drive tumor growth. Drugs that block NK-1R (like the anti-nausea drug aprepitant) are already approved for other uses and could potentially be tested against thyroid cancer.

Does this mean Substance P causes thyroid cancer?

Not necessarily. Higher expression in cancer does not prove it causes the cancer. But if SP/NK-1R signaling promotes tumor growth, blocking it could be a new treatment strategy.

Read More on RethinkPeptides

Cite This Study

RPEP-04878·https://rethinkpeptides.com/research/RPEP-04878

APA

Isorna, Inmaculada; Esteban, Francisco; Solanellas, Juan; Coveñas, Rafael; Muñoz, Miguel. (2020). The substance P and neurokinin-1 receptor system in human thyroid cancer: an immunohistochemical study.. European journal of histochemistry : EJH, 64(2). https://doi.org/10.4081/ejh.2020.3117

MLA

Isorna, Inmaculada, et al. "The substance P and neurokinin-1 receptor system in human thyroid cancer: an immunohistochemical study.." European journal of histochemistry : EJH, 2020. https://doi.org/10.4081/ejh.2020.3117

RethinkPeptides

RethinkPeptides Research Database. "The substance P and neurokinin-1 receptor system in human th..." RPEP-04878. Retrieved from https://rethinkpeptides.com/research/isorna-2020-the-substance-p-and

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Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.