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Updated: Jan 20, 2026

Combining Multiplex Fluorescence In Situ Hybridization with Fluorescent Immunohistochemistry on Fresh Frozen or Fixed Mouse Brain Sections
Published on: June 25, 2021
Correlation between immunohistochemistry and RICTOR fluorescence in situ hybridization amplification in small cell
Ildiko Krencz1, Anna Sebestyen1, Judit Papay1
11st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary H-1085.
Abstract:
Small cell lung carcinoma (SCLC) accounts for approximately 15% of all lung cancers and remains a challenging disease, with no significant improvement in the field of targeted therapies. The RICTOR gene (rapamycin-insensitive companion of mTOR [mammalian target of rapamycin]), which encodes a key structural (scaffold) protein of mTOR complex 2), has recently been identified as one of the most frequently amplified genes and a potential therapeutic target in SCLC. The aim of this study was to compare immunohistochemical (IHC) expression of Rictor and phospho-Akt (a downstream target of mTOR complex 2) with RICTOR amplification as detected by fluorescence in situ hybridization (FISH) in SCLC. RICTOR FISH and Rictor and phospho-Akt IHC staining were performed on 100 formalin-fixed, paraffin-embedded SCLC samples. RICTOR amplification was detected in 15 samples (15%). IHC positivity for Rictor and phospho-Akt was observed in 37 (37%) and 42 (42%) samples, respectively. Considering FISH as the diagnostic standard, the sensitivity and specificity of Rictor IHC were 93% and 73%, whereas the sensitivity and specificity of phospho-Akt IHC were 80% and 65%, respectively. Rictor expression was higher in distant metastases than in primary tumor samples and lymph node metastases. There was no association between RICTOR amplification and clinical outcome. However, high expression of either Rictor or phospho-Akt was associated with significantly decreased overall survival. In conclusion, IHC expression of Rictor correlates highly with RICTOR amplification. Therefore, Rictor IHC can be used as a cost-effective method to select patients for RICTOR FISH and, potentially, for mTORC1/2 inhibitor therapy.
Insights
Immunohistochemistry (IHC) for Rictor protein is a reliable and cost-effective method to identify small cell lung cancer (SCLC) patients with RICTOR gene amplification, aiding in selecting candidates for targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Small cell lung carcinoma (SCLC) is a challenging cancer with limited targeted therapy options.
- The RICTOR gene, encoding a component of mTOR complex 2, is frequently amplified in SCLC and represents a potential therapeutic target.
Purpose of the Study:
- To compare immunohistochemical (IHC) expression of Rictor and phospho-Akt with RICTOR gene amplification in SCLC.
- To evaluate Rictor IHC as a potential surrogate for RICTOR amplification detection.
Main Methods:
- 100 SCLC samples underwent RICTOR fluorescence in situ hybridization (FISH) and Rictor/phospho-Akt IHC staining.
- FISH was used as the gold standard for RICTOR amplification detection.
Main Results:
- RICTOR amplification was found in 15% of SCLC samples.
- Rictor IHC showed high sensitivity (93%) and specificity (73%) for detecting RICTOR amplification.
- High Rictor or phospho-Akt expression correlated with decreased overall survival, but RICTOR amplification did not correlate with clinical outcome.
Conclusions:
- Rictor IHC expression strongly correlates with RICTOR amplification in SCLC.
- Rictor IHC serves as a cost-effective method for patient selection for RICTOR FISH and potential mTORC1/2 inhibitor therapy.
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