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

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.

Keywords

• FISH
• EGFR
• KRAS
• C-ERBB2
• Küçük hücreli dışı akciğer karsinomu

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

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.

Keywords

• FISH
• EGFR
• KRAS
• C-ERBB2
• Non-small cell lung carcinoma

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