BackgroundThe IGF-1R signaling pathways have cross-talk with HER-2 signaling pathways and was thought to be one of the resistance mechanism intrastuzumab therapy. This research was proposed to analyze the correlation between IGF-1R and HER-2 expression with mitosis count andhistopathological grade in invasive breast carcinoma of no special type.MethodsThis research was a cross-sectional design. A total of fifty-five invasive breast carcinoma of no special type cases diagnosed in theAnatomical Pathology Centre Diagnostic of Medical Faculty of Andalas University in a period of 2014-2015 were collected and stainedimmunohistochemically with IGF-1R and HER-2 antibodies. IGF-1R and HER-2 expression were examined and their correlation with mitosiscount and histopathological grade were statistically analyzed with T-test, Oneway Anova and Chi-Square test.ResultsIGF-1R cytoplasm and membranous expression were found positive in 18.2% and 34.5% cases respectively, meanwhile, HER-2 expressionswere found positive in 23.6% cases of invasive breast carcinoma of no special type. There were significant correlations between IGF-1Rcytoplasm expression with mitosis count (p=0.049). There were no significant correlations between IGF-1R membranous expression withmitosis count (p=0.641) with histopathological grade (p=1.00). There were no significant correlations between HER-2 expression withmitosis count (p=0,495) and histopathological grade (p=1.000).ConclusionIGF-1R expressions have a significant correlation with mitosis count rather than HER-2 expressions. Inhibition it’s signaling pathways mayhave therapeutic value in breast carcinoma. Combination therapy of anti-HER-2 and anti-IGF-1R are expected to overcome resistance withtrastuzumab in HER-2 positive breast carcinoma
Peritoneal cytology is crucial in the diagnosis and staging of abdominal and pelvic malignancies. Diagnostic pitfalls can be avoided by having an understanding of the different methods of sampling, a familiarity with cytomorphology of the various specimen types, adequate clinical history, and an ability to prepare cell blocks and/or review other prior or concurrent specimens. Ovarian cancer is the second most frequent type of gynecological malignancy but the most lethal. While high-grade serous carcinoma is the most common histological subtype, mucinous carcinoma of the ovary (MCO) was believed to constitute around 4% of ovarian malignancies. It is critical to diagnose these rare tumors correctly to ensure proper treatment, avoid mortality, and preserve fertility for young women.
About 75% of breast carcinoma is invasive carcinoma of no special type (NST) and between 20%-30% of breast carcinoma is HER-2 positive. HER-2 overexpression now is a predictive factor for targeted therapy with anti-HER-2 agent like trastuzumab (herceptin). However, primary (de novo) resistance with trastuzumab occured in 65% patients and secondary resistance occured in 70% patients who have had good initial response. IGF-1R expression have been reported high in many malignancies including breast carcinoma. Researches have showed that IGF-1R signaling pathway have a crosstalk with HER-2 signaling pathway and was thought to become one of resistance mechanism in anti-HER-2 targeted therapy. This research was a retrospective observational cross-sectional study with a total 55 samples. Expression of IGF-1R and HER-2 was evaluated immunohistochemically. A strong positive IGF-1R cytoplasm and membranous expression was 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 was no correlation between IGF-1R membranous and cytoplasm expression with histological grade (p=1,000) and there was no correlation between HER-2 expression with mitosis count (p=0,495) and histological grade (p=1,000). IGF-1R expression has more potential effect in mitosis compared with HER-2 expression. Inhibition it's signaling pathway 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.
Resistensi pengobatan yang ditandai dengan kekambuhan lokal-regional serta timbulnya efek samping sistemik yang hebat terhadap terapi non-bedah salah satu penyebab tingginya angka kematian pada penderita karsinoma payudara. Kemoterapi berbasis anthracycline diketahui lebih efektif mencegah kekambuhan lokal-regional namun berisiko terhadap kegagalan jantung sehingga dibutuhkan penanda spesifik untuk pemberian kemoterapi ini. TOPO2A merupakan molekul target direk anthracycline. Ekspresi protein dan kelainan gen TOPO2A diduga dapat dijadikan indikator pemberian anthracycline akan tetapi hasil penelitian saat ini masih ditemukan kontroversi. Kelainan gen TOPO2A selalu dikaitkan dengan amplifikasi gen HER-2 karena keduanya terletak pada kromosom yang sama dan diduga berhubungan dengan sensitifitas terhadap kemoterapi berbasis anthracycline. Penelitian ini merupakan penelitian observasional dengan desain cross sectional. Sampel penelitian sebanyak 50 kasus karsinoma payudara invasif tidak spesifik yang dilakukan re-evaluasi terhadap jumlah mitosis dan derajat histopatologik. Ekspresi TOPO2A dan HER-2 dinilai secara imunohistokimia masing-masing pada inti dan membran sel, kemudian dinilai hubungannya dengan jumlah mitosis dan derajat histopatologik dengan menggunakan T-test, Oneway Anova dan Chi square test. Uji statistik bermakna jika nilai p<0,05. Overekspresi TOPO2A dan HER-2 masing-masing ditemukan pada 18 kasus (36%) dan 10 kasus (20%). Analisis statistik menunjukkan hubungan yang bermakna antara ekspresi TOPO2A dengan jumlah mitosis (p=0.004) dan derajat histopatologik (p=0.006), tidak terdapat hubungan yang bermakna antara ekspresi HER-2 dengan jumlah mitosis (p=0.72) dan derajat histopatologik (p=1,000). Ekspresi protein TOPO2A secara konsisten berhubungan dengan karsinoma payudara yang agresif dibandingkan dengan ekspresi HER-2 dan dapat digunakan sebagai penanda prognostik terhadap pemberian kemoterapi berbasis anthracycline.
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