ANALISIS EKSPRESI INSULIN-LIKE GROWTH FACTOR TYPE-1 RECEPTOR DAN HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2 TERHADAP FAKTOR HISTOPATOLOGIK KARSINOMA PAYUDARA INVASIF TIDAK SPESIFIK

Yessy, Setiawati (2018) ANALISIS EKSPRESI INSULIN-LIKE GROWTH FACTOR TYPE-1 RECEPTOR DAN HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2 TERHADAP FAKTOR HISTOPATOLOGIK KARSINOMA PAYUDARA INVASIF TIDAK SPESIFIK. Masters thesis, Universitas Andalas.

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Abstract

ANALISIS EKSPRESI INSULIN-LIKE GROWTH FACTOR TYPE-1 RECEPTOR DAN HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2 TERHADAP FAKTOR HISTOPATOLOGIK KARSINOMA PAYUDARA INVASIF TIDAK SPESIFIK Oleh: Yessy Setiawati (1420312037) (Dibawah Bimbingan: Dr. dr. Rosfita Rasyid, M.Kes dan dr. Aswiyanti Asri, M.Si.Med, SpPA) Abstrak Pendahuluan: Resistensi terapi diduga merupakan salah satu penyebab tingginya angka kematian pada karsinoma payudara saat ini. Overekspresi HER-2 merupakan faktor prediktif terhadap terapi target dengan anti-HER-2 seperti trastuzumab (herceptin) pada karsinoma payudara HER-2 positif. Akan tetapi, resistensi primer (de novo) terhadap trastuzumab ditemukan pada 65% penderita dan resistensi sekunder terjadi pada 70% penderita yang awalnya mempunyai respon terapi yang baik. Penelitian menunjukkan adanya cross-talk antara jalur sinyal IGF-1R dengan HER-2 dan diduga menjadi salah mekanisme terjadinya resistensi terhadap trastuzumab. Metode: Penelitian ini merupakan penelitian observasional dengan desain cross sectional. Sampel penelitian sebanyak 55 kasus karsinoma payudara invasif tidak spesifik yang didiagnosis di Sentra Diagnostik Patologi Anatomik Fakultas Kedokteran Universitas Andalas periode tahun 2014-2015 yang dilakukan pulasan imunohistokimia dengan antibodi IGF-1R dan HER-2. Ekspresi IGF-1R dan HER-2 dinilai hubungannya dengan faktor histopatologik jumlah mitosis dan derajat histopatologik secara statistik. Data dianalisis sesuai dengan jenis data dengan menggunakan T-test, Oneway Anova dan Chi Square test. Uji statistik dianggap bermakna jika nilai p<0,05. Hasil: Ekspresi IGF-1R sitoplasma dan membran positif ditemukan masing-masing pada 18,2% dan 34,5% kasus sedangkan ekspresi HER-2 positif ditemukan pada 23,6% kasus karsinoma payudara invasif tidak spesifik. Terdapat hubungan yang bermakna antara ekspresi IGF-1R sitoplasma dengan jumlah mitosis (p=0.049). Akan tetapi, tidak terdapat hubungan yang bermakna antara ekspresi IGF-1R membran dengan jumlah mitosis (p=0,641). Tidak terdapat hubungan yang bermakna antara ekspresi IGF-1R membran dan sitoplasma dengan derajat histopatologik (p=1,000) serta tidak terdapat hubungan yang bermakna antara ekspresi HER-2 dengan jumlah mitosis (p=0,495) dan derajat histopatologik (p=1,000). Diskusi: Ekspresi IGF-R mempunyai pengaruh lebih kuat terhadap jumlah mitosis dibandingkan dengan HER-2. Penghambatan jalur sinyal IGF-1R dapat bermanfaat pada penatalaksanaan karsinoma payudara. Kombinasi terapi anti-IGF-1R dan anti-HER-2 dapat mengatasi resistensi trastuzumab pada karsinoma payudara HER-2 positif. Kata kunci: Karsinoma payudara invasif tidak spesifik, IGF-1R dan HER-2 ANALYSIS OF INSULIN-LIKE GROWTH FACTOR TYPE-1 RECEPTOR AND HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2 EXPRESSIONS WITH HISTOPATHOLOGICAL FACTORS OF INVASIVE BREAST CARCINOMA OF NO SPECIAL TYPE By: Yessy Setiawati (1420312037) (Under Supervision of: Dr. dr. Rosfita Rasyid, M.Kes dan dr. Aswiyanti Asri, M.Si.Med, SpPA) Abstract Introduction: Drug’s resistance is thought as one cause of high breast cancer mortality rate recently. HER-2 overexpression is a predictive factor for anti-HER-2 agents targeted therapy, for example trastuzumab (herceptin), in HER-2 positive breast carcinoma. However, primary (de novo) resistance with trastuzumab was occured in 65% patients and secondary resistance was occured in 70% patients who have had good initial response. Researches have showed that IGF-1R signaling pathways have cross-talk with HER-2 signaling pathways and was thought to become one of resistance mechanism in trastuzumab therapy. Methods: This research was a retrospective observational cross-sectional study with a total of fifty five cases invasive breast carcinoma of no special type that were diagnosed in The Anatomical Pathology Center of Diagnostic, Medicine Faculty of Andalas University at year 2014-2015. Samples were examined and stained with IGF-1R and HER-2 antibodies immunohistochemically. Correlation of IGF-1R and HER-2 expressions with histopathological factors that are number of mitosis and histopathological grade were statistically analyzed. In accordance with type of data, T-test, Oneway Anova and Chi Square test were used. Statistical tests were considered significance if p-value <0.05. Results: A strong positive IGF-1R cytoplasm and membranous expression were found in 18,2% and 34,5% cases, respectively. HER-2 expression was positive in 23,6% cases. IGF-1R cytoplasm expression was correlated significantly with mitosis count (p=0.049). There was no correlation between IGF-1R membranous expression with mitosis count (p=0,641). There were no correlation between IGF-1R membranous and cytoplasm expression with histological grade (p=1,000) and there were no correlation between HER-2 expression with mitosis count (p=0,495) and histological grade (p=1,000). Discussion: IGF-1R expressions have more potential effect in mitosis compared with HER-2 expressions. Inhibition it’s signaling pathways may have therapeutic value in breast carcinoma. Combination therapy of anti-HER-2 with anti-IGF-1R could overcome resistancy of trastuzumab in HER-2 positive breast carcinoma. Keywords: Invasive breast carcinoma of NST, IGF-1R and HER-2 expression.

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