Research Article
BibTex RIS Cite

Clinicopathological and prognostic significance of immunohistochemical C-ERBB2 positivity in non-small cell lung cancers

Year 2024, , 28 - 35, 28.03.2024
https://doi.org/10.18663/tjcl.1341970

Abstract

Aim: Lung cancer is the most common cause of cancer deaths worldwide. Individualized treatment options occurred with the development of targeted therapy. The best-known genetic alterations which are important in therapy guidance of non-small cell lung cancer (NSCLC) are KRAS, EGFR, ALK, C-ERBB2, PIK3CA, BRAF, ROS1 and AKT. The significance of C-ERBB2 that plays an important role in treatment and prognosis of breast and gastric carcinoma is not known enough in NSCLC. Therefore, a pilot study is designed to show the role and importance of overexpression of C-ERBB2 in NSCLC and to identify the current prevalence and distribution of C-ERBB2 in Turkey in case it may be used as targeted therapy in near future for NSCLC.
Material and Methods: In this study, 258 cases, were diagnosed with NSCLC between 2005-2014 in the pathology department of Haydarpasa Numune Training and Research Hospital, were included. H&E stained microscopic slides of cases were re-examined and stained for C-ERBB2 immunohistochemically. Score 1, 2 or 3 was given according to the intensity and completeness of staining. C-ERBB2 scores were then compared with clinicopathological and prognostic features.
Results: C-ERBB2 positivity was observed in 6,2% of cases. The positivity was comparatively higher in adenocarcinomas. A statistically significant relationship was not detected between C-ERBB2 positivity and clinicopathological (tumor type, subtype, grade, lymph node metastasis, lymphovascular invasion, pleural invasion, and tumor size) and prognostic features (mortality, overall survival, progression-free survival, recurrence).
Conclusion: In this study, C-ERBB2 overexpression was detected in adenocarcinomas almost to a statistically significant degree. However, in NSCLC statistically significant relationship could not be demonstrated between clinicopathological and prognostic parameters and immunohistochemical positivity of C-ERBB2. For this reason, cases with scores of 2 and 3 should be reexamined with in-situ hybridisation or other genetic tests and additional studies should be performed to determine the clinicopathological and prognostic parameters and the response to anti-HER2 treatment.

References

  • Ferlay, J., Colombet, M., Soerjomataram, I., Parkin, D. M., Piñeros, M., Znaor, A., & Bray, F. (2021). Cancer statistics for the year 2020: An overview. International journal of cancer, 10.1002/ijc.33588. Advance online publication. (doi.org/10.1002/ijc.33588).
  • Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: a cancer journal for clinicians, 61(2), 69–90. (doi.org/10.3322/caac.20107).
  • Siegel, R., Ma, J., Zou, Z., & Jemal, A. (2014). Cancer statistics, 2014. CA: a cancer journal for clinicians, 64(1), 9–29. (doi.org/10.3322/caac.21208)
  • Travis, W. D., Brambilla, E., Noguchi, M., Nicholson, A. G., Geisinger, K. R., Yatabe, Y., Beer, D. G., Powell, C. A., Riely, G. J., Van Schil, P. E., Garg, K., Austin, J. H., Asamura, H., Rusch, V. W., Hirsch, F. R., Scagliotti, G., Mitsudomi, T., Huber, R. M., Ishikawa, Y., Jett, J., Yankelewitz, D. (2011). International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 6(2), 244–285. (doi.org/10.1097/JTO.0b013e318206a221)
  • Dacic S. (2011). Molecular diagnostics of lung carcinomas. Archives of pathology & laboratory medicine, 135(5), 622–629. (doi.org/10.5858/2010-0625-RAIR.1).
  • Cheng, H., Xu, X., Costa, D. B., Powell, C. A., & Halmos, B. (2010). Molecular testing in lung cancer: the time is now. Current oncology reports, 12(5), 335–348. (doi.org/10.1007/s11912-010-0118-z).
  • Yurdakul A, Çalışır H DFVA. Akciğer kanserinin histolojik tiplerinin dağılımı. Toraks Derg. 2002;3:59–65.
  • Dacic, S., Shuai, Y., Yousem, S., Ohori, P., & Nikiforova, M. (2010). Clinicopathological predictors of EGFR/KRAS mutational status in primary lung adenocarcinomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 23(2), 159–168. (doi.org/10.1038/modpathol.2009.154)
  • Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-2139. (doi:10.1056/NEJMoa040938).
  • Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497-1500. (doi:10.1126/science.1099314)
  • Yılmazbayhan D, Özlük Y. Küçük Hücreli Dışı Akciğer Karsinomlarında Patoloji. Journal of Clinical and Analytical Medicine. 2004. p. 8–15.
  • Koeppen HK, Wright BD, Burt AD, et al. Overexpression of HER2/neu in solid tumours: an immunohistochemical survey. Histopathology. 2001;38(2):96-104. (doi:10.1046/j.1365-2559.2001.01084.x).
  • Boku N. HER2-positive gastric cancer. Gastric Cancer. 2014;17(1):1-12. (doi:10.1007/s10120-013-0252-z).
  • Takenaka M, Hanagiri T, Shinohara S, et al. The prognostic significance of HER2 overexpression in non-small cell lung cancer. Anticancer Res. 2011;31(12):4631-4636.
  • Ugocsai K, Mándoky L, Tiszlavicz L, Molnár J. Investigation of HER2 overexpression in non-small cell lung cancer. Anticancer Res. 2005;25(4):3061-3066.
  • Tateishi M, Ishida T, Mitsudomi T, Kaneko S, Sugimachi K. Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma. Eur J Cancer. 1991;27(11):1372-1375. (doi:10.1016/0277-5379(91)90012-3).
  • Mazières J, Peters S, Lepage B, et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol. 2013;31(16):1997-2003. (doi:10.1200/JCO.2012.45.6095).
  • Arcila ME, Chaft JE, Nafa K, et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res. 2012;18(18):4910-4918. (doi:10.1158/1078-0432.CCR-12-0912)
  • Heinmöller P, Gross C, Beyser K, et al. HER2 status in non-small cell lung cancer: results from patient screening for enrollment to a phase II study of herceptin. Clin Cancer Res. 2003;9(14):5238-5243.
  • Buttitta F, Barassi F, Fresu G, et al. Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. Int J Cancer. 2006;119(11):2586-2591. (doi:10.1002/ijc.22143)
  • Xu Y, Wang L, Zheng X, Liu G, Wang Y, Lai X, Li J. Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients. Mol Clin Oncol. 2013 May;1(3):487-492.
  • Suzuki M, Shiraishi K, Yoshida A, et al. HER2 gene mutations in non-small cell lung carcinomas: concurrence with Her2 gene amplification and Her2 protein expression and phosphorylation. Lung Cancer. 2015;87(1):14-22. (doi:10.1016/j.lungcan.2014.10.014).
  • Korrapati V, Gaffney M, Larsson LG, et al. Effect of HER2/neu expression on survival in non-small-cell lung cancer. Clin Lung Cancer. 2001;2(3):216-219. doi:10.3816/clc.2001.n.006
  • Brabender J, Danenberg KD, Metzger R, et al. Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival. Clin Cancer Res. 2001;7(7):1850-1855.
  • Riudavets M, Sullivan I, Abdayem P, Planchard D. Targeting HER2 in non-small-cell lung cancer (NSCLC): a glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations. ESMO Open. 2021 Oct;6(5):100260.

Küçük hücre dışı akciğer kanserlerinde immünhistokimyasal C-ERBB2 pozitivitesinin klinikopatolojik ve prognostik önemi

Year 2024, , 28 - 35, 28.03.2024
https://doi.org/10.18663/tjcl.1341970

Abstract

Amaç: Meme ve mide karsinomlarında tedavi ve prognozda önemli rol oynayan C-ERBB2’nin küçük hücreli dışı akciğer karsinomlarında (KHDAK) önemi bilinmemektedir. Bu nedenle C-ERBB2’nin KHDAK’lardaki rolünü ve önemini ortaya koymak, ileride hedefe yönelik tedavide olası kullanım durumunda Türkiye’deki hastalardaki durumunu saptamaya yönelik pilot bir çalışma amaçlanmıştır.
Gereç ve Yöntemler: Bu çalışmaya, Haydarpaşa Numune Eğitim ve Araştırma Hastanesi Patoloji Bölümü’nde 2005-2014 tarihleri arasında KHDAK tanısı almış 258 olgu alındı. Vakalara ait hematoksilen eozin (H&E) boyalı lamlar değerlendirildi ve immünhistokimyasal C-ERBB2 boyama uygulandı. Boyanma şiddetine, komplet ve/veya inkomplet boyanmasına göre 1, 2, ve 3 olarak skorlandırıldı. C-ERBB2 skorları, klinikopatolojik ve prognostik özellikler ile karşılaştırıldı.
Bulgular: Vakaların %6.2’sinde C-ERBB2 pozitif olarak saptanmıştır. Pozitivite adenokarsinomlarda nispeten daha yüksektir. C-ERBB2 pozitivitesi ile klinikopatolojik (tümör tipi, subtipi, “grade”i, lenf nodu metastazı, lenfovasküler invazyon, plevral invazyon ve tümör çapı) ve prognostik özellikler (mortalite, genel sağkalım, progresyonsuz sağkalım, nüks) arasında istatistiksel olarak anlamlı bir ilişki saptanmamıştır.
Sonuçlar: Çalışmamızda C-ERB B2 overekspresyonu adenokarsinomlarda anlamlıya yakın dereceden daha fazla görülmüştür. Ancak KHDAK immünhistokimyasal C-ERBB2 pozitivitesinin, çalışmamızda ele aldığımız klinikopatolojik ve prognostik parametreler ile istatistiksel olarak anlamlı bir ilişkisi saptanmamıştır. Bu nedenle skor 2 ve 3 olan olgular insituhibridizasyon veya diğer genetik mutasyon incelemeleri ile tekrar test edilmeli; C-ERBB2 overekspresyon ya da mutasyonu olan hastaların klinikopatolojik ve prognostik parametreleri ile anti-HER2 tedavisine verecekleri cevabın belirlenmesi için ek çalışmalar yapılmalıdır.

References

  • Ferlay, J., Colombet, M., Soerjomataram, I., Parkin, D. M., Piñeros, M., Znaor, A., & Bray, F. (2021). Cancer statistics for the year 2020: An overview. International journal of cancer, 10.1002/ijc.33588. Advance online publication. (doi.org/10.1002/ijc.33588).
  • Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: a cancer journal for clinicians, 61(2), 69–90. (doi.org/10.3322/caac.20107).
  • Siegel, R., Ma, J., Zou, Z., & Jemal, A. (2014). Cancer statistics, 2014. CA: a cancer journal for clinicians, 64(1), 9–29. (doi.org/10.3322/caac.21208)
  • Travis, W. D., Brambilla, E., Noguchi, M., Nicholson, A. G., Geisinger, K. R., Yatabe, Y., Beer, D. G., Powell, C. A., Riely, G. J., Van Schil, P. E., Garg, K., Austin, J. H., Asamura, H., Rusch, V. W., Hirsch, F. R., Scagliotti, G., Mitsudomi, T., Huber, R. M., Ishikawa, Y., Jett, J., Yankelewitz, D. (2011). International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 6(2), 244–285. (doi.org/10.1097/JTO.0b013e318206a221)
  • Dacic S. (2011). Molecular diagnostics of lung carcinomas. Archives of pathology & laboratory medicine, 135(5), 622–629. (doi.org/10.5858/2010-0625-RAIR.1).
  • Cheng, H., Xu, X., Costa, D. B., Powell, C. A., & Halmos, B. (2010). Molecular testing in lung cancer: the time is now. Current oncology reports, 12(5), 335–348. (doi.org/10.1007/s11912-010-0118-z).
  • Yurdakul A, Çalışır H DFVA. Akciğer kanserinin histolojik tiplerinin dağılımı. Toraks Derg. 2002;3:59–65.
  • Dacic, S., Shuai, Y., Yousem, S., Ohori, P., & Nikiforova, M. (2010). Clinicopathological predictors of EGFR/KRAS mutational status in primary lung adenocarcinomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 23(2), 159–168. (doi.org/10.1038/modpathol.2009.154)
  • Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-2139. (doi:10.1056/NEJMoa040938).
  • Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497-1500. (doi:10.1126/science.1099314)
  • Yılmazbayhan D, Özlük Y. Küçük Hücreli Dışı Akciğer Karsinomlarında Patoloji. Journal of Clinical and Analytical Medicine. 2004. p. 8–15.
  • Koeppen HK, Wright BD, Burt AD, et al. Overexpression of HER2/neu in solid tumours: an immunohistochemical survey. Histopathology. 2001;38(2):96-104. (doi:10.1046/j.1365-2559.2001.01084.x).
  • Boku N. HER2-positive gastric cancer. Gastric Cancer. 2014;17(1):1-12. (doi:10.1007/s10120-013-0252-z).
  • Takenaka M, Hanagiri T, Shinohara S, et al. The prognostic significance of HER2 overexpression in non-small cell lung cancer. Anticancer Res. 2011;31(12):4631-4636.
  • Ugocsai K, Mándoky L, Tiszlavicz L, Molnár J. Investigation of HER2 overexpression in non-small cell lung cancer. Anticancer Res. 2005;25(4):3061-3066.
  • Tateishi M, Ishida T, Mitsudomi T, Kaneko S, Sugimachi K. Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma. Eur J Cancer. 1991;27(11):1372-1375. (doi:10.1016/0277-5379(91)90012-3).
  • Mazières J, Peters S, Lepage B, et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol. 2013;31(16):1997-2003. (doi:10.1200/JCO.2012.45.6095).
  • Arcila ME, Chaft JE, Nafa K, et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res. 2012;18(18):4910-4918. (doi:10.1158/1078-0432.CCR-12-0912)
  • Heinmöller P, Gross C, Beyser K, et al. HER2 status in non-small cell lung cancer: results from patient screening for enrollment to a phase II study of herceptin. Clin Cancer Res. 2003;9(14):5238-5243.
  • Buttitta F, Barassi F, Fresu G, et al. Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. Int J Cancer. 2006;119(11):2586-2591. (doi:10.1002/ijc.22143)
  • Xu Y, Wang L, Zheng X, Liu G, Wang Y, Lai X, Li J. Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients. Mol Clin Oncol. 2013 May;1(3):487-492.
  • Suzuki M, Shiraishi K, Yoshida A, et al. HER2 gene mutations in non-small cell lung carcinomas: concurrence with Her2 gene amplification and Her2 protein expression and phosphorylation. Lung Cancer. 2015;87(1):14-22. (doi:10.1016/j.lungcan.2014.10.014).
  • Korrapati V, Gaffney M, Larsson LG, et al. Effect of HER2/neu expression on survival in non-small-cell lung cancer. Clin Lung Cancer. 2001;2(3):216-219. doi:10.3816/clc.2001.n.006
  • Brabender J, Danenberg KD, Metzger R, et al. Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival. Clin Cancer Res. 2001;7(7):1850-1855.
  • Riudavets M, Sullivan I, Abdayem P, Planchard D. Targeting HER2 in non-small-cell lung cancer (NSCLC): a glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations. ESMO Open. 2021 Oct;6(5):100260.
There are 25 citations in total.

Details

Primary Language Turkish
Subjects Pathology
Journal Section Research Article
Authors

Ayşe Nur Toksöz Yıldırım 0000-0003-1708-0003

Fügen Vardar Aker 0000-0002-7092-3391

Murat Erkan 0000-0003-3900-1150

Publication Date March 28, 2024
Published in Issue Year 2024

Cite

APA Toksöz Yıldırım, A. N., Vardar Aker, F., & Erkan, M. (2024). Küçük hücre dışı akciğer kanserlerinde immünhistokimyasal C-ERBB2 pozitivitesinin klinikopatolojik ve prognostik önemi. Turkish Journal of Clinics and Laboratory, 15(1), 28-35. https://doi.org/10.18663/tjcl.1341970
AMA Toksöz Yıldırım AN, Vardar Aker F, Erkan M. Küçük hücre dışı akciğer kanserlerinde immünhistokimyasal C-ERBB2 pozitivitesinin klinikopatolojik ve prognostik önemi. TJCL. March 2024;15(1):28-35. doi:10.18663/tjcl.1341970
Chicago Toksöz Yıldırım, Ayşe Nur, Fügen Vardar Aker, and Murat Erkan. “Küçük hücre dışı akciğer Kanserlerinde immünhistokimyasal C-ERBB2 Pozitivitesinin Klinikopatolojik Ve Prognostik önemi”. Turkish Journal of Clinics and Laboratory 15, no. 1 (March 2024): 28-35. https://doi.org/10.18663/tjcl.1341970.
EndNote Toksöz Yıldırım AN, Vardar Aker F, Erkan M (March 1, 2024) Küçük hücre dışı akciğer kanserlerinde immünhistokimyasal C-ERBB2 pozitivitesinin klinikopatolojik ve prognostik önemi. Turkish Journal of Clinics and Laboratory 15 1 28–35.
IEEE A. N. Toksöz Yıldırım, F. Vardar Aker, and M. Erkan, “Küçük hücre dışı akciğer kanserlerinde immünhistokimyasal C-ERBB2 pozitivitesinin klinikopatolojik ve prognostik önemi”, TJCL, vol. 15, no. 1, pp. 28–35, 2024, doi: 10.18663/tjcl.1341970.
ISNAD Toksöz Yıldırım, Ayşe Nur et al. “Küçük hücre dışı akciğer Kanserlerinde immünhistokimyasal C-ERBB2 Pozitivitesinin Klinikopatolojik Ve Prognostik önemi”. Turkish Journal of Clinics and Laboratory 15/1 (March 2024), 28-35. https://doi.org/10.18663/tjcl.1341970.
JAMA Toksöz Yıldırım AN, Vardar Aker F, Erkan M. Küçük hücre dışı akciğer kanserlerinde immünhistokimyasal C-ERBB2 pozitivitesinin klinikopatolojik ve prognostik önemi. TJCL. 2024;15:28–35.
MLA Toksöz Yıldırım, Ayşe Nur et al. “Küçük hücre dışı akciğer Kanserlerinde immünhistokimyasal C-ERBB2 Pozitivitesinin Klinikopatolojik Ve Prognostik önemi”. Turkish Journal of Clinics and Laboratory, vol. 15, no. 1, 2024, pp. 28-35, doi:10.18663/tjcl.1341970.
Vancouver Toksöz Yıldırım AN, Vardar Aker F, Erkan M. Küçük hücre dışı akciğer kanserlerinde immünhistokimyasal C-ERBB2 pozitivitesinin klinikopatolojik ve prognostik önemi. TJCL. 2024;15(1):28-35.


e-ISSN: 2149-8296

The content of this site is intended for health care professionals. All the published articles are distributed under the terms of

Creative Commons Attribution Licence,

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.