Correlation between immunohistochemistry and RICTOR fluorescence in situ hybridization amplification in small cell lung carcinoma

Ildiko Krencz, Anna Sebestyen, Judit Papay, Yanyan Lou, Gabrielle F. Lutz, Tracy L. Majewicz, Andras Khoor

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)74-80
Number of pages7
JournalHuman Pathology
Volume93
DOIs
StatePublished - Nov 2019

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Small Cell Lung Carcinoma
Fluorescence In Situ Hybridization
Immunohistochemistry
Sirolimus
Neoplasm Metastasis
Sensitivity and Specificity
Paraffin
Formaldehyde
Genes
Lung Neoplasms
Therapeutics
Lymph Nodes
Staining and Labeling
Costs and Cost Analysis
Survival
Neoplasms
Proteins
TOR complex 2

Keywords

  • Fluorescence in situ hybridization
  • Immunohistochemistry
  • Phospho-Akt
  • RICTOR
  • Small cell lung carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Correlation between immunohistochemistry and RICTOR fluorescence in situ hybridization amplification in small cell lung carcinoma. / Krencz, Ildiko; Sebestyen, Anna; Papay, Judit; Lou, Yanyan; Lutz, Gabrielle F.; Majewicz, Tracy L.; Khoor, Andras.

In: Human Pathology, Vol. 93, 11.2019, p. 74-80.

Research output: Contribution to journalArticle

Krencz, Ildiko ; Sebestyen, Anna ; Papay, Judit ; Lou, Yanyan ; Lutz, Gabrielle F. ; Majewicz, Tracy L. ; Khoor, Andras. / Correlation between immunohistochemistry and RICTOR fluorescence in situ hybridization amplification in small cell lung carcinoma. In: Human Pathology. 2019 ; Vol. 93. pp. 74-80.
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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.",
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AU - Krencz, Ildiko

AU - Sebestyen, Anna

AU - Papay, Judit

AU - Lou, Yanyan

AU - Lutz, Gabrielle F.

AU - Majewicz, Tracy L.

AU - Khoor, Andras

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N2 - 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.

AB - 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.

KW - Fluorescence in situ hybridization

KW - Immunohistochemistry

KW - Phospho-Akt

KW - RICTOR

KW - Small cell lung carcinoma

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