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. 2023 Jun 30;12(6):1245-1255.
doi: 10.21037/tlcr-22-621. Epub 2023 Jun 13.

Concordance between cryobiopsy and forceps biopsy specimens in assessment of immunohistochemistry staining for non-small cell lung carcinoma

Kanako Nishimatsu  1   2 , Yuji Matsumoto  1   3 , Jumpei Kashima  2 , Tatsuya Imabayashi  1 , Keigo Uchimura  1 , Hideaki Furuse  1 , Ken Masuda  3 , Yuki Shinno  3 , Yusuke Okuma  3 , Tatsuya Yoshida  3 , Yasushi Goto  3 , Hidehito Horinouchi  3 , Noboru Yamamoto  3 , Takaaki Tsuchida  1 , Yuichiro Ohe  3 , Yasushi Yatabe  2
Affiliations

Concordance between cryobiopsy and forceps biopsy specimens in assessment of immunohistochemistry staining for non-small cell lung carcinoma

Kanako Nishimatsu et al. Transl Lung Cancer Res. .

Abstract

Background: Cryobiopsy is recently being promoted for biopsy of tumors in the lung periphery in precision medicine for lung cancer; the obtained tissue samples have been reported to be more useful compared to those obtained using forceps, because of the larger volume and higher quality. However, the influence of freezing and thawing of tissues when performing cryobiopsy on the results of immunohistochemistry (IHC) has not been completely understood.

Methods: In this study, consecutive patients who underwent diagnostic bronchoscopy with cryobiopsy for peripheral pulmonary lesions (PPLs) at our institution between June 2017 and November 2021 were reviewed retrospectively. Specimens of diagnosed cases of unresectable or recurrent non-small cell lung carcinoma (NSCLC) were selected. We compared the results of IHC assessment for programmed death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), and human epidermal growth factor receptor 3 (HER3) in cryobiopsy specimens versus conventional forceps biopsy specimens from the same site in the same procedure.

Results: Twenty-four of 40 patients were male (60%). The most frequent histologic type of cancer was adenocarcinoma (n=31, 77.5%), followed by NSCLC (n=4, 10%), squamous cell carcinoma (n=3, 7.5%), and others (n=2, 5%). The concordance rates of the tumor proportion scores (TPSs) for PD-L1, IHC score for HER2 and, IHC scores for HER3 were 85%, 72.5%, and 75%, respectively; the weighted kappa were 0.835, 0.637, and 0.697, respectively.

Conclusions: Freezing and thawing associated with cryobiopsy had virtually no effect on the results of IHC. We suggest that cryobiopsy specimens would therefore be ideal for precision medicine and translational research.

Keywords: Cryobiopsy; human epidermal growth factor receptor 2 (HER2); human epidermal growth factor receptor 3 (HER3); immunohistochemistry (IHC); lung cancer.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-621/coif). YO serves as an unpaid editorial board member of Translational Lung Cancer Research from January 2020 to December 2023. YM reports research fund from Hitachi and honoraria from Olympus, AstraZeneca, NOVARTIS, COOK, AMCO, Thermo Fisher Scientific, Erbe Elektromedizin GmbH, Fujifilm, Chugai, Eli Lilly, Merck and Takeda. TI reports grants from Hitachi High-Tech Corporation and honoraria from COOK, Chugai pharma, Eli Lilly, Olympus, Novartis pharma, Fujifilm and Thermo Fisher Scientific K.K. KU reports grants from Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Nos. JP22K15698 JP19K16966), and receives payments for lectures from Novartis, Thermo Fisher Scientific, AstraZeneca and Chugai. TY reports lecture fees from AstraZeneca, Chugai, Ono, Eli Lilly, and Takeda, and research funds from AMGEN, AstraZeneca, Takeda, Daiichi-Sankyo, Ono, MSD, AbbVie, Novartis, Chugai, Novartis, Chugai, Merck, Blueprint, and BMS. YG reports grants from AZK, Pfizer, Abbvie, Eli Lilly, Pfizer, Bristol Myers Squibb, Ono, Novartis, Kyorin, DaiichiSankyo, Novartis, and Prefered Networ, honoraria from Eli Lilly, Chugai,Taiho, Boehringer Ingelheim, Ono, Bristol Myers Squibb, Pfizer, MSD, Novartis. Merck, and Thermo Fischer, participation on an advisory board from AstraZeneca, Chugai, Boehringer Ingelheim, Eli Lilly, Taiho, Pfizer, Novartis, Guardant Health Inc., Illumina, DaiichiSankyo, Ono Pharmaceutical, Bristol Myers Squibb, and MSD, and leadership in Cancer Net Japan, JAMT. HH serves as a consultant to AstraZeneca, Eli Lilly, Chugai, Roche, Ono, BMS, and MSD, and receives lecture fees from AstraZeneca, MSD, Eli Lilly Ono, BMS, Chugai, Roche, Kyowa-Kirin, and Novartis, and research funds from MSD, AstraZeneca, BMS, Ono, Merck Biopharma, Daiichi-Sankyo, Janssen, Genomic Health, Chugai, Roche, and Novartis. Yuichiro Ohe receives lecture fees from AstraZeneca and Chugai, and research funds from AstraZeneca, Chugai, Eli Lilly, Ono, BMS, Kyorin, Dainippon-Sumitomo, Pfizer, Taiho, Novartis, Takeda, Kissei, Daiichi-Sankyo, Janssen, and LOXO. YY reports honoraria for lectures from MDS, Chugai-pharma, AstraZeneca, Novartis, Pfizer, Thermo Fisher Science, and Amgen. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Patients flow diagram.
Figure 2
Figure 2
Pearson’s correlation coefficient for PD-L1. The horizontal and vertical axes indicate the tumor proportion scores of the forceps biopsy and cryobiopsy, respectively. There is a strong correlation between the two specimens (R2=0.831). TPS, tumor proportion score; PD-L1, programmed death-ligand 1.
Figure 3
Figure 3
A representative case of favor adenocarcinoma showing complete concordances in the results of the respective IHC. The upper images show serial sections of cryobiopsy specimens (A-D ×10 magnification) whereas the lower ones show those of forceps specimens (E-H ×10 magnification). Hematoxylin and eosin-stained sections demonstrate that the tumor cells proliferate in a solid pattern (A,E). The tumor proportion scores for programmed death-ligand 1 are both 95% (B,F). Incomplete and faintly perceptible membrane staining of >10% of the tumor cells is observed; thus, the IHC scores for anti-HER 2 are both 1+ (C,G). Moderate complete membrane staining is observed in >10% of tumor cells; hence, IHC scores for HER3 are both 2+ (D,H). IHC, immunohistochemistry; HER, human epidermal growth factor receptor.
Figure 4
Figure 4
A representative case of adenocarcinoma showing discordance in the results of the IHC scores for anti-HER3. The upper images show serial sections of cryobiopsy specimens (A ×1 magnification, B-D ×20 magnification) whereas the lower ones show those of forceps specimens (E ×2 magnification, F-H ×20 magnification). The sizes of the cryobiopsy and forceps biopsy specimens are 3.7 mm × 5.4 mm (A) and 0.8 mm × 0.6 mm (E), respectively. The cryobiopsy specimen retains a well-defined architecture (B) whereas the forceps biopsy specimen is somewhat crushed (F). The tumor proportion scores for programmed death-ligand 1 are both <1% (C,G). Although the IHC score for HER3 can be determined as 2+ for the cryobiopsy specimen (D), it is difficult to evaluate the IHC score for the forceps biopsy specimen due to loss of tumor cells during thin sectioning and is determined as 0 (H). IHC, immunohistochemistry; HER, human epidermal growth factor receptor.
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