Validity of using immunohistochemistry to predict treatment outcome in patients with non-small cell lung cancer not otherwise specified
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Histology samples are important for the appropriate administration of tumor type-specific cytotoxic and molecular-targeted therapies for the treatment of non-small cell lung cancer (NSCLC). When biopsy samples lack a definite morphology, a diagnosis can be selected from three subtypes based on immunohistochemistry (IHC) results, as follows: favor adenocarcinoma (ADC), favor squamous cell carcinoma (SQC), or not otherwise specified (NOS)-null. In terms of patient outcome, however, the validity of IHC-based classifications remains unknown.
A large series of 152 patients with advanced NSCLC whose diagnoses had been made based on morphological findings and who had been homogeneously treated were enrolled. We used IHC staining (TTF-1, SP-A, p40, and CK5/6) to examine tumor samples and refined the diagnoses. We then analyzed the pathological subgroups according to the IHC staining results.
IHC profiling resulted in 50% of the cases being classified as favor ADC, 31% being classified as favor SQC, and 19% being classified as NOS-null groups. Compared with the favor ADC and favor SQC groups, the NOS-null group had a significantly poorer outcome. Pemetrexed-containing platinum regimens produced a response rate similar to that of other platinum doublet regimens in the favor ADC group (44% vs. 46%), whereas it produced a poorer response in the favor SQC group (0% vs. 52%) and the NOS-null group (0% vs. 24%). The favor ADC group tended to have a higher percentage of EGFR positivity and ALK positivity than the favor SQC group (25% vs. 11% and 7% vs. 0%, respectively).
These findings support the use of immunohistological subtyping of NSCLC biopsy specimens to select patient-appropriate treatments.
KeywordsImmunohistochemistry Non-small cell lung cancer Not otherwise specified Pemetrexed Outcome
This work was not funded by a grant from any companies or organizations.
Compliance with ethical standards
Conflict of interest
Dr. Kirita reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chugai Pharmaceutical, personal fees from MSD, personal fees from Novartis Pharma, personal fees from Pfizer, personal fees from Roche, and personal fees from Boston, outside the submitted work. Dr. Udagawa reports personal fees from AstraZeneca, grants and personal fees from MSD, personal fees from Taiho, personal fees from Amco, grants and personal fees from AbbVie, personal fees from Chugai Pharmaceutical, personal fees from Bristol-Myers Squibb, personal fees from Ono Pharmaceutical, grants from Daiichi Sankyo, and grants from AMGEN, outside the submitted work. Dr. Matsumoto reports grants from Chugai Pharmaceutical Co., Ltd., grants from Novartis Pharma K.K., and grants from Merck Serono Co., Ltd., outside the submitted work. Dr. Yoh reports grants and personal fees from Ono Pharmaceutical, grants and personal fees from Taiho Pharmaceutical, grants and personal fees from Chugai Pharma, grants and personal fees from AstraZeneca, grants and personal fees from Lilly Japan, personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, grants from Pfizer, grants and personal fees from MSD, grants from Bristol-Myers Squibb, and grants from Bayer, outside the submitted work. Dr. Niho reports personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Chugai, grants and personal fees from AstraZeneca, grants from Merck Serono, and grants and personal fees from Pfizer, outside the submitted work. Dr. Goto reports grants and personal fees from Eli Lilly, during the conduct of the study; grants and personal fees from AbbVie Stemcentrx, grants from Ignyta, personal fees from F. Hoffmann-La Roche, grants and personal fees from Life Technologies Japan, grants from Oxonc, personal fees from Otsuka Pharmaceutical, grants and personal fees from RIKEN GENESIS, personal fees from SRL, grants and personal fees from Sumitomo Dainippon Pharma, grants and personal fees from AstraZeneca, grants from Astellas Pharma, grants from Amgen Astellas BioPharma, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Daiichi Sankyo, grants from Eisai, grants and personal fees from Kyowa Hakko Kirin, grants and personal fees from MSD, grants and personal fees from Merck Serono, grants and personal fees from Novartis Pharma, grants and personal fees from ONO Pharmaceutical, grants and personal fees from Pfizer, grants and personal fees from Taiho, grants and personal fees from Takeda Pharmaceutical, and grants from Janssen Pharmaceutical, outside the submitted work. None of the other authors has any conflict of interest to declare.
The study was conducted with the approval of the Institutional Review Boards of the National Cancer Center. The IRB approval number for this study was 2016-125. All the methods were performed in accordance with the approved guidelines.
All the specimens were collected after obtaining written comprehensive informed consent from the patients.
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