الفهرس 
TitleOnly 14 pages are availabe for public view
 |  | from | 153 |  |  |
| | | from | 153 | | |
Abstract
Worldwide, breast cancer is a common cancer in women and the incidence of BC in the developed countries is higher but the virtual mortality rate is the highest in the developing countries. In Egypt, according to the results of the National Population-Based Cancer Registry Program, BC has the second rank with rate of 15.4 % after liver cancer (23.8 %) for both sexes. In Eastern Libya, BC represented 41.5% of all women cancers. The concern about the challenge of BC comes into sight due to its genetic heterogeneity. The main risk factors for developing BC include age, reproductive factors, family history, lifestyle factors and menopausal status. These factors can be strongly independent predictors. Breast cancer is evaluated and monitored by mammographic density that refers to the extent of radio-dense fibro-glandular tissue in the breast. Based on the clinical appearance, histological type and tumour markers expression [gene expression profile of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2)], breast cancer is divided into various molecular subtypes.
The identification of HER2 status as a clinical biomarker is crucial for prognosis but mostly for identifying patients who will benefit from HER2 targeted therapies. HER2 status should be determined in all patients with invasive BC on the basis of one or more HER2 test results (negative, equivocal, or positive). IHC is an invasive semi-quantitative technique which detects HER2 positive cells in surgically removed tissue. The main disadvantages of IHC are false-negative and false-positive HER2 status assessments. HER2 gene amplification is detected by FISH in the case of equivocal (score 2+) HER2. Nevertheless, the technique FISH is also invasive, irreproducible, and requires special equipment and reagents. Consequently, a simple, non-invasive, quantitative, repeatable HER2 detection test that reflects the characteristics of tumours at diagnosis and allows monitoring after surgical intervention is required. The soluble circulating ECD of HER2 which is cleaved by matrix metalloproteases and shed into bloodstream has been suggested as a surrogate marker that correlates with overexpression of tissue HER2 and worse prognosis in metastatic BC.
ELISA is quantitative and non-invasive technique that can detect the concentration of serum HER2 ECD. Biosensors are analytical devices that convert a biological event into an electronic signal and can distinguish a specific biomarker. Immunosensors have been well established as valid alternatives to classical analytical methods for detection of cancer biomarkers. Various types of nanoparticles were established for increasing LOD of serum HER2 when the tumour marker is slightly altered. Additional co-receptor of HER2 is MUC1-C that interacts with HER2 and other receptor tyrosine kinases. CA 15-3 is used to anticipate detection of recurrences in BC patients and as an additional tool in evaluating therapeutic response of advanced disease. Moreover, preoperative levels of CA 15-3 have a significant independent relation to outcome in patients with early BC.
The aim of the current study was to compare the efficiency and the sensitivity of the conventional tissue HER2 immunohistochemistry with both ELISA and AuNPs in detecting tHER2 and sHER2 and to correlate them with clinicopathological parameters, and sCA15-3 level.
Summary, Conclusions and Recommendations
91
The study included 47 BC patients, five recurrent breast tumours patients, and twenty healthy controls. Demographic and clinicopathological data were collected to correlate with sHER2, tHER2, and CA 15-3 biomarkers. tHER2 and sHER2 are detected by IHC, ELISA, and biosensors to validate sHER2 as a surrogate marker that might replace or complement the current techniques in use for tHER2 estimation.
The level of tHER2 as detected by ELISA significantly differed among groups (p = 0.045) and significantly decreased (p = 0.02) with higher Body Mass Index (BMI) in equivocal HER2 (2+) group. A significant direct correlation (r = 0.9, p = 0.037) observed between tHER2 and sHER2 levels as detected by AM in HER2 (3+) group. Further on, tHER2 detected by ELISA significantly differed (p = 0.017) by the classification of BC into triple negative (TN), liminal A, luminal B, and HER2 groups. Whereas, a significant direct correlation (r = 0.857, p = 0.014) observed between tHER2 and sHER2 levels detected by ELISA in HER2 group. On the other hand, sHER2 level detected by AM showed high sensitivity and specificity in differentiating between TN from luminal A at cut off value > 9.26 ng/ml (p = 0.003) and HER2 at cut off value of 9.6 ng/ml (p = 0.0450). At cut off value of > 1.67 ng/ml, tHER2 detected by ELISA classified TN from luminal A (p = 0.04), luminal A from luminal B (p = 0.003), HER2 from luminal A (p = 0.011), HER2 (2+) from HER2 (1+) (p = 0.016), and HER2 (3+) from HER2 (1+) (p = 0.004). Moreover, sCA15-3 (p = 0.048) significantly differed among groups.
CA 15-3 significantly differed between the studied groups regardless HER2 status or BC molecular subtypes. Also, no relation was observed between HER2 and patients’ outcomes or clinicopathological parameters or NPI.
AuNPs based biosensor was used to detect HER2 in standards and serum of BC patients. The detection linearity ranged from 1624 to 101.5 ng and the lowest detection limit was 2.6 ng. However, the spectrum inferred interference noise from serum proteins, buffer components, and the slide materials that mandate further optimisations in the future studies.