41^st World Cancer Conference August 01-02, 2022 Zurich, Switzerland

Biography:

Ms Nilima S. Desai joined Division of Immunohistochemistry in 1992 as a Research fellow. She is involved in clinical research aspects of Immunohistochemistry and molecular pathology. She has presented her data in 20 National and International meetings, notable among them being 5^th International symposium on Impact of Biotechnology on Cancer Diagnostic and Prognostic indicators by International Society for Preventive Oncology at Geneva, Switzerland in 2000. “Seeking Excellence in Breast Cancer Care” American Cancer Society sponsored and organized by John Hopkins Institute Nursing, Baltimore, USA in 1999; and Reach to Recovery International 2^nd Asia Pacific UICC breast cancer support conference in 2004, Singapore. She has undergone observer-ship in Immunohistochemistry laboratory at Memorial Sloan Kettering Cancer Centre (MSKCC), New York, USA for one week in October 1999. “Her2 in breast cancer by IHC” paper abstract in UICC (2006) abstract book. Poster paper presented and Abstract published in “Regulators of Apoptosis in Human Breast Cancer” in UICC World Cancer Congress, Int. J. of Cancer CD Rom supplement 2008 PUB-354, 27-31^st August 2008, Geneva, Switzerland. Invited Speaker at BIT’s Life Science World Cancer Congress, WCBC-2011, Nov. 16-18, Guangzhou, China for the oral presentation “Clinical Significance of Prognostic Molecular Markers in Breast Carcinoma”. Invited, Participated and awarded Diploma in NordiQC workshop in Diagnostic Immunohistochemistry at Aalborg, Denmark from 18-20 Sept. 2013. National meeting held at New Delhi during Nov. 20-24, 2013. Abstract published in Indian Cancer Congress. Faculty at MSc. Cancer Biology 2013, Gujarat University affiliated, Gujarat Cancer & Research Institute, Ahmedabad. She has done Poster presentation on “Expression of MDM2, Cyclin E and basal subtype marker CK5/6 in Breast Carcinoma” during 17-18 March 2015. Tucson Symposium 2015 at Tucson, Arizona, USA during 17-18 March 2015.

Abstract:

Background: The incidence of breast cancer at The Gujarat Cancer & Research Institute, Ahmedabad, India is approx. 23.76% according to hospital base registry 1997 and it is rising and a major health problem affecting a large number of women. Among women with early-stage breast cancer treated with lumpectomy and local radiotherapy, 10% to 20% will experience local recurrence and 30% to 40% will develop distant metastatic disease, which is often fatal. So, a need exists for identifying prognostic markers that accurately predict long term outcome in those patients, thus permitting rational choices among therapeutic options such as adjuvant chemotherapy, surgical resection, radiation therapy, hormonal therapy, and application of newly discovered experimental therapeutics. Predictive biomarkers are greatly needed that can help guide clinicians and patients in treatment related decisions about the necessity (or lack thereof) for adjuvant chemotherapy, hormonal therapy, and new treatments as they become available.

Aim: The aim of the present study was to investigate the prognostic significance of ER, PR, Her2 Neu, Bcl2, BAG1, P53, Ki67, Topoisomerase II alpha, FOXA1 and GATA-3 binding protein, MDM2 protein, Cyclin E and basal subtype marker Cytokeratin 5/6 in primary breast carcinomas and further compared with Clinicopathological parameters.

Methods and materials: Paraffin blocks were obtained from the Pathology Department of our Institute. Study conducted during the period 1997-2016. Routinely morphological diagnosis done by our histopathologist on H&E sections was noted. The clinical information regarding age, menopausal status, tumor size, lymph node status, stage, histological type and grade and treatment offered were obtained from the case files maintained at medical record department. Disease staging was done according to TNM Classification of malignant tumors, T (tumor), N (nodal) & M (distant metastasis) Staging system of (AJCC) American Joint Committee on Cancer, Staging Manual 6^th edition, New York, 2002, Springer. The treatment of these patients was decided by the clinicians. The patients were treated with surgery followed by (CT) chemotherapy (CMF) cyclophosphamide, methotraxate, 5-florouracil, or (FAC) 5-fluorouracil, doxorubicin, & cyclophosphamide, & (AC) doxorubicin, cyclophosphamide and/or Radiotherapy (RT) and/or Hormonal Therapy (HT) (Tamoxifen). Majority of the (93%) patients treated with surgery followed by CT and RT.

Immunohistochemical localisation

In brief 3 mm thin paraffin sections were cut and after treating with milk for 5 mins heated at 60ºC overnight. Slides were then stained in automatic Immunostainer Ventana Bench Mark XT Tm Machine where deparaffinization, the endogenous peroxidase activity, Bluing and DAB are done automatically according to the protocol already feed. Sections were then washed and mounted in DPX outside. Known positive controls for each of these antibodies as well as negative controls (i.e. sections in which the primary antibody were substituted by non-immune mouse serum were also stained in each run. Using Ventana BenchMark XT automated Immunostainer Estrogen Receptor (ER), Progesterone Receptor (PR), Her2 Neu, CK5/6 were evaluated. Bcl2 Novocastra, UK NCL-bcl-2 1:40, P53 Dakocytomation CA USA DO-7 1:25, BAG-1 Dakocytomation, CA, USA KS-6C8 1:100, Topoisomerase IIalpha Dakocytomation, CA, USA SWT3D1 1:50, Ki67 Antigen DAKO, Glostrup, Denmark MIB-1 1:25, CerbB2 Novocastra CB11 1:30, MDM2, Cycline E were evaluated. ER procured from (Dako, 1:100), PR (Dako, 1:50), Her2Neu, Mdm2 from Lab Vision Corporation, Neomarkers, USA. Used in 1:50 giving Nuclear staining, Cycline E from Thermo Scientific Lab Vision in dilution 1:10 showing Cytoplasmic staining, Biogenex (1:30) and CK5/6 (1: 10) (Ab 2 Clone B4) Thermo scientific Neomarker, UK.

Scoring interpretation

The semi quantitative scoring was done as follows: tumors with marker staining in <10% cells considered negative, staining in 10-20% cells considered 1+ and staining in 20-50% cells considered 2+ and staining in >50% cells considered 3+.

Statistical analysis

The data were statistically analyzed using SPSS statistical software version 13. The two-tailed chi-square test was used to assess the association between two parameters. Correlation between two parameters was calculated using Spearman’s correlation coefficient (r) method. Overall Survival (OS) were evaluated using the Kaplan-Meier method. The log rank test was used to assess the prognostic significance of OS. P values less than 0.05 were considered significant.

Results: Our earlier study reveals Patients who subsequently developed metastases had significantly high MV counts than patients without metastatic disease (p<0.001). Patients who subsequently died of the disease had significantly high mean microvessels counts than patients who remained alive at the end of 5 years (p<0.001). As density of factor VIII antigen staining increased the survival decreased (p<0.001). All the patients having >25 MV per 200x field had tumour recurrence faster as compared with patients having <25 MV (p<0.02). MV count correlates with the prediction for metastasis and poor survival. Such an indicator would be useful in selection of a subgroup of patients with breast cancer who are at high risk for having occult metastasis at presentation and subsequently would benefit from aggressive therapy.

Protein expression of Bcl2, BAG-1 and P53 were studied by immunohistochemical localisation on paraffin embedded tumour tissue sections as well as by molecular methods of breast cancer patients. Protein expression of Bcl2, BAG-1 and P53 was noted in 57%, 68% and 61% in tumours of breast tumours (carcinoma patients), respectively. Further, a significant decrease in Bcl2 expression was noted with increase in tumour size, disease stage and tumour grade in younger patients. In univariate survival analysis, Bcl2 overexpression significantly associated with better overall survival in lymph node negative patients. Moreover, in trivariate analysis patients with three marker positivity had reduced overall survival as compared to patients with one or two marker positivity followed by negative subgroup.

Molecular study reveals When markers were inter correlated a trend of positive correlation was observed between p53 exon 5 & 7 (P=0.069) while no such correlation was observed between Bcl2 gene with Exon 5 & 7. Expression of exon 5 was found to be higher in patients expressing p53 (92%) protein also a trend of Inverse correlation was observed between Exon 5 and PR (P=0.06). Within LN status subgroup patients, a significant positive correlation was noted between LN positive patients and p53 exon 5 and 7 expression (P=0.027). A trend of positive correlation was also observed with Bcl2 gene and protein within Older age group patients (>48 years; P=0.068). No such correlation was observed with in LN status subgroup patients.

In other study, sixty-two patients of primary breast carcinoma were enrolled. Out of total patients, ninety two percent tumors were invasive ductal carcinoma, 2% Medullary, and Metaplastic carcinoma respectively and, 5% tumors had Lobular subtype. Nodal involvement was observed in 35% patients and 31% having histological grade III. ER and PR positivity was observed in 68% and 81% of the tumors respectively. 37% Her2/Neu positivity was noted.

We studied the expression of FOX1 and GATA-3 binding protein FOXA1 expression was documented as follows; positive 1+ (16%), 2+ (26%) and 3+ (55%). While GATA-3 was detected in 21% and CK5/6 expression was observed in 29% of the total sections. We observed that FOXA1 expression was inversely associated with Age, LN stage and grade while GATA-3 expression showed inverse association with lymph node and Her2 over expression. Significant correlation was observed between basal marker CK5/6 and grade (P<0.02). FOXA1 was positively correlated with Her2 overexpression (P<0.001). FOXA1 was found to be associated with reduced overall survival (P<0.032).

Protein expression of MDM2, Cyclin E and Basal sub type marker Cytokeratin5/6 was observed in 79%, 18%, and 29% respectively. Fifty three percent patients were in early stage, 45% patients had age >51 years, 92% patients had IDC and 31% patients had HG III tumors and 35% patients had LN status negative. Among them, 68% patients had ER positive tumors, 81% patients had PR positive tumors and 37% patients had 3+ Her2 Neu positivity. A significant inverse correlation was noted between LN status (p=0.055) and MDM2. A trend of inverse correlation was also noted with established clinicopathological markers ER, PR and Her2 Neu. A significant positive correlation was noted between Ck5/6 and grade (P=0.020). A trend of reduced overall survival was observed with in breast cancer patients with Mdm2, Ck5/6 and Cyclin E markers.

Conclusion: The fact that breast cancer is not a uniform cancer entity but consists of several different subtypes with different molecular profiles, biological behaviour, and risk profiles poses a challenge for the clinical management. Prognostic and predictive factors constitute important tools for the individualization of breast cancer therapy to provide efficient treatment and to spare patients with excellent low-risk profiles from unwanted side effects of overtreatment. The established clinicopathologic markers, in particular ER and HER2, have clearly defined clinical applicability, but deficiencies in the methodologies of assessment may still affect their use. Additional tools are required to facilitate clinical decision-making processes especially for the optimal treatment of early hormone receptor-positive breast cancer.

MV count correlates with the prediction for metastasis and poor survival. Such an indicator would be useful in selection of a subgroup of patients with breast cancer who are at high risk for having occult metastasis at presentation and subsequently would benefit from aggressive therapy Thus, Bcl2 negativity and BAG-1 and P53 positivity indicated aggressive phenotypes in breast cancer patients. p53 exon 5 & 7 expression was found to be associated with hormonal receptors, Down regulation of p53 protein noted as compared to incidence of p53 gene expression. p53 protein expression was associated with hormone receptors negativity. FOXA1 was found to be associated with reduced overall survival. A trend of reduced overall survival was observed with in breast cancer patients with Mdm2, Ck5/6 and Cyclin E markers. A change from the traditional approach of using only established markers appears to be an inevitable next step in newly diagnosed patients with breast cancer however more patients to be analyzed.

Biography:

Xiaoxia Yin is a professor in Guangzhou University, China.

Abstract:

Neoadjuvant Chemotherapy (NAC) in breast cancer patients has considerable prognostic and treatment potential and can be tailored to individual patients as part of precision medicine protocols. This work reviews recent advances in artificial intelligence so as to enable the use of radiogeomics for the accurate NAC analysis and prediction. The work addresses a new problem in radiogenomics mining: How to combine structural radiomics information and non-structural genomics information for accurate NAC prediction. This requires the automated extraction of parameters from structural breast radiomics data, and finding non-structural feature vectors with diagnostic value, which then are combined with genomics data acquired from exocrine bodies in blood samples from a cohort of cancer patients to enable accurate NAC prediction. A self-attention-based deep learning approach along with an effective multi-channel tumour image reconstruction algorithm of high dimensionality is proposed. The aim is to generate non-structural feature vectors for accurate prediction of the NAC responses by combining imaging datasets with exocrine body related genomics analysis

Biography:

Pechersky, Alexander is an Associate Professor at North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia. His achievements include the original articles devoted to the influence of partial androgen dеficiency among aging men (PADAM) on the development of benign prostatic hyperplasia, prostate cancer and metabolic syndrome, diagnostics and treatment of partial androgen deficiency of aging men, regeneration, immune system, carcinogenesis, cicatrization, desensitization, immunological tolerance and antitumor

Abstract:

Germinative mutations determine hereditary predisposition to various diseases, initiating their early manifestation and rapid progression. At the same time, the proportion of germinative mutations is significantly less compared to the somatic mutations prevailing in humans that occur in various cells throughout their life (during ontogenesis). The appearance of malignant tumors, type 2 diabetes, hypercholesterolemia and other diseases / pathological conditions in aging people is accompanied by the development of corresponding somatic mutations. Somatic mutations provide genetic fixation of compensatory-adaptive reactions (functional at the initial stage) developing in aging people in response to impaired tissue renewal / regeneration, decreased production of sex hormones and other pathological conditions. The mechanism of somatic mutations is similar to the genetic changes occurring in cells during their differentiation, and is due to the ranking of genes with the removal of non-functioning DNA sections. This is associated with irreversible changes in malignant and other cells (for example, those that have become insulin-resistant). Timely restoration of tissue renewal (regeneration) and adequate replacement of sex hormones in aging people can significantly reduce the risk of developing compensatory adaptive responses and, accordingly, subsequent somatic mutations that cause irreversible cellular changes.

Biography:

Rong-Hui Zheng MD, Chief Physician, Deputy Director of Radiotherapy Department of Affiliated Cancer Hospital & Institute of Guangzhou Medical University(and leader of the Section 2）,master’s supervisor, Academic Leader of Head and Neck cancer society. Director of National Standardized Resident Doctor Training of Radiation-Oncology Professional Base. Executive Deputy Director of Popularization education Base of Nasopharyngeal Carcinoma in Guangdong Province. Chairman of the Head and Neck Cancer Branch of Guangdong -Provincial Health-Science Promotion Association. Committee member of Cancer Hyperthermia Branch of China Anti-Cancer Association. Committee member of Hyperthermia Branch of China-Japan Medical Science and Technology Communication Association. Chairman of the Radiation Oncology Branch of Guangzhou Medical Association. Research focus on comprehensive treatment in head and neck cancer(i.e. in radiotherapy) .

Abstract:

Purpose: To explore the optimization of clinical target volume (CTV) delineation in lower neck to protect the thyroid gland in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). Materials and methods: Part I (670 patients were included): We tried to find out the extremely low risk sub-areas of lower neck lymph nodes （LNs） metastasis by dividing into six sub-areas （Figure 1）. Part II (40 patients were included): According to the research results of extremely low risk sub-areas CTV in part I from different N stages patients, the extremely low risk subareas were in lower neck were shrunk, then we made new radiotherapy plans, and last we evaluated the irradiation doses of thyroid in new plans comparing with the control plans (not shrink the lower neck CTV). Result: In Part I, we found that positive （short diameter≥4mm） rate of lower neck LNs was 0% all in 1-5 subregions for N0 patients, in 1-4 subregions for N1 patients and 1-3 subregions for N2 patients. In Part II, results showed that the median thyroid dose and V50 after shrinking lower neck CTV area decreased to 35.3% and 36.9% comparing with 54.1%（P=0. 000）and 58.3%（P=0. 000） before CTV shrinking; the dose of common carotid artery (V60), esophagus (Dmean) and trachea (Dmean) decreased as well. Conclusion: The CTV of the lower neck of NPC has a shrunk space: 1-4 subregions can be omitted in N1 patients and 1-3 subregions can be omitted in N2 patients to protect the thyroid and other OARs in lower neck. However, further clinical researches remain needed to confirm whether the dose reductions can be transformed into clinical reductions of toxic reactions and the improvements of quality of life

Biography:

Ravi P Sahu is a professor in Wright State University. The major research interests of my laboratory are We explore molecular biology, immunology, and pharmacological approaches, including microvesicle particles analysis, gene deletion/overexpression, gene array, qPCR, western blotting, and flow cytometry with multiple novel cellular systems, relevant mouse models including genetic knockout and transgenic, as well as human samples for our research. Our basic and translational research projects involve collaborations with colleagues, including Physician-Scientists and Pathologists, and primarily use melanoma, lung and pancreatic cancer models.

Abstract:

Lung cancer remains one of the highly aggressive malignancies associated with poor prognosis and increased mortality rates. Of two major types, non-small cell lung cancer (NSCLC) is the most prevalent type and detected in 80-85% lung cancer cases. Several studies have shown the involvement of multiple signaling pathways in affecting the growth and treatment efficacy using NSCLC models. To that end, the roles of microRNAs (miRs) in essentially all biological processes are evident. The altered expression of miRs has been documented in various disease conditions, including cancer. While multiple mechanisms have been identified in mediating miRs effects, the involvement of miR-149-5p in Platelet-activating factor-receptor (PAFR)-induced effects on lung cancer growth and therapeutic potential has not been studied. Given the oncogenic and tumor-suppressive roles of miRNA-149-5p, and the oncogenic effect of PAFR signaling in various cancer models, our studies sought to determine the potential link between miR-149-5p and PAFR signaling in NSCLC models. Using A549 and H1299 cell lines, we first verified the tumor- suppressive role of miR-149-5p and the growth proliferative effect of PAFR signaling. Our next studies demonstrated that overexpression of miR-149-5p significantly attenuated PAFR agonist, CPAF-mediated increased proliferation of NSCLC cells. These findings were confirmed by the expression analysis of miR-149-5p, cyclin D1, and forkhead box protein M1 (FOXM1) via qRT- PCR. Our next studies examined the effects of the PAFR and miR-149-5p on targeted therapy (i.e., erlotinib and gefitinib) responses. We found that both these therapies inhibit the survival of A549 and H1299 cell lines in a dose- and time-dependent manner. Importantly, activation of the PAFR significantly blocked this effect. These findings indicate that miR-149-5p blocks PAFR-mediated increased cell proliferation and that PAFR activation attenuates the cytotoxic effects of targeted therapy.