A Multicenter Study of the Impact of Body Mass Index (BMI) on the incidence of Pathologic Complete Response (pCR) Among Saudi Patients with locally advanced Breast cancer (LABC) post Neoadjuvant Chemotherapy (NAC).

PURPOSE: Obesity was reported to be a poor prognostic factor for breast cancer. There is a growing evidence of increasing prevalence of obesity among Saudi women across all age groups (44%). Since the prognostic significance of obesity was not studied in Saudi patients with breast cancer, the aim of this study was to evaluate the impact of BMI on pCR in LABC patients post NAC. PATIENTS AND METHODS: This is a retrospective study between May 2005 to July 2010; 246 consecutive female patients who were diagnosed of LABC (Stage II & III) and underwent surgery in three tertiary care centers, representative of the Kingdom of Saudi Arabia (King Saud Medical City, Riyadh; King Abdullah Hospital, Mecca and King Fahad Specialist Hospital, Dammam) were included in this study. All included patients have received NAC (Anthracycline/Taxane based combination chemotherapy and ± Herceptin). Patients who were diagnosed to have stage IV breast cancer due to presence of distant metastasis were excluded. Patients were categorized as normal (BMI <25 kg/m2), overweight (BMI of 25 to <30 kg/m2) and obese (BMI >30 kg/m2). pCR was defined as no invasive cancer in the breast or axillary tissue. Univariate and multivariate analysis were used to evaluate the statistical associations between pCR and BMI with respect to the other previously established prognostic factors, namely age, tumor grade, stage, ER/ PR /Her-2neu status, molecular subtypes, and lympho-vascular invasion (LVI). RESULTS: The median age was 50 years (range 24-68). Molecular subtypes were as follows: luminal A; 23.2%, luminal B; 45.1%, triple negative; 16.7% and Her-2 neu positive; 15%. Infiltrating ductal carcinoma represents the majority of our cohort (92.7%). Eighty-six (35%) were stage II and 160 (65%) were stage III. Intermediate and high-grade malignancies were found in 52% and 44.3% of the patients respectively. Positive lymph vascular invasion was detected in 41.5%. Obese patients constitute 55.7% of our cohort. Pathologic complete response was achieved in 62 patients (25.2%). In Univariate analysis LVI and overweight /obesity were negatively correlated with pCR (P= 0.037 and 0.000 respectively) while tumor grade was positively correlated with pCR (P= 0.008). In multivariate analysis, Overweight/ obesity was the only significant independent factor correlating with pCR (P=0.000). No impact of BMI has been demonstrated on both disease-free survival (DFS) and overall survival (OS) (P=0.93, 0.18 respectively). CONCLUSION: In this study, Overweight/Obesity (which represent more than half of the patients =81.3 %) had a negative impact on pCR in Saudi patients with LABC treated with NAC. This poorer outcome in patients with abnormal weight (Overweight/Obesity) necessitates further prospective studies of this risk factor in order to optimize the care of this group of patients.

The Expression of FOXE-1 and STIP-1 in Papillary Thyroid Carcinoma and Their Relationship with Patient Prognosis.

BACKGROUND & OBJECTIVE: Most patients with papillary carcinoma of the thyroid gland (PTC) havefavorable outcome,but sinceit has severe capability to invade the nearby tissues, there isa great risk of regional and distal lymph-nodes (LNs) metastases related to poor prognostic parameters, early recurrences, and distant metastasis that lead to bad patient outcome. Discovering other prognostic biomarkers for this cancer helps to detect early recurrences, invasion, expecting patient outcome, and possible use as therapeutic-targets for it. The fork-head-box-E-1(FOX-E-1), with the alternative name of thyroid-transcriptionfactor-2 (TTF-2), is one of thetranscription factors familiesthat is huge and containsa special fork-head-domain. It has a significant role in the differentiation and maturation of thyroid-follicular cells. Stress-induced phosphor-protein-1 (STIP-1), withthe alternative name ofheat-shock-protein-(HSP)organizing protein,is a 62.6-kD protein, with three parts of tetra-trico-peptide repeats (TPR), and is capable of interaction with heat-shock proteins forming structures that haveplethora of roles in variable cellular processes;e.g., cell cycles regulations, transcriptions, and RNA splicing.The current study aimed at exploring the relationship between FOXE-1 and STIP-1 expressions, the clinicopathological parameters, prognosis, and survival of patients with PTC. METHODS: The current studyexplored FOXE-1 and STIP-1 expressions by the immunohistochemical methods in 36 paraffin blocks retrieved from 36 patients of PTC, analyzed the relationships between their levels of expression,clinicopathological parameters, prognosis, and survival of patients. RESULTS: The high expression levels forboth FOXE-1 and STIP-1 in PTC were associated with larger size of the tumor, extra-thyroidal extension, vessels invasion, LNs spread (P <0.001), presence of distant metastases (P values = 0.005 and 0.012, respectively) and higher stages of the cancer (P values =0.012 and 0.042, respectively).The FOXE-1 over-expression was associated with shortened distant metastases free survival (DMFS) and shortened five-year overall survival rates (OS) (P <0.001). CONCLUSION: Patients withadvanced PTC andunfavorable prognosis had high levels of both FOXE-1 and STIP-1 expressions.

The prognostic significance of p53, p63 and her2 expression in non-muscle-invasive bladder cancer in relation to treatment with bacille Calmette-Guerin.

OBJECTIVE: To investigate whether the immunohistochemical expression of p53, p63 and her2/neu is correlated with the prognosis of tumour recurrence and progression in patients with non-muscle invasive (NMI) bladder cancer. PATIENTS AND METHODS: In all, 88 patients diagnosed with NMI transitional cell carcinoma of the bladder in a Urology Department from May 2009 to April 2014 were included in the study. Paraffin-embedded specimens were obtained by transurethral resection of the bladder tumours. Sections on haematoxylin and eosin-stained slides were examined histologically and tumour grade was classified according to the World Health Organisation system (2004) Mostofi classification. The sections were evaluated using p63, p53 and her2/neu immunohistochemical staining before and after immunotherapy with bacille Calmette-Guerin (BCG), and patients were followed up for 36 months in the Urology Department. RESULTS: For tumour grade there was a significant relationship with the overexpression of p53 (P = 0.010), her2 (P = 0.025) and negativity of p63 (P = 0.025). There was no significant relationship between p53 or her2/neu overexpression and tumour stage. However, there was a significant correlation (P = 0.005) between p63 negativity and tumour stage. There was a significant relationship between p53 (P = 0.01), her2/neu (P = 0.025) overexpression and p63 negativity (P = 0.005) and tumour recurrence and progression. CONCLUSION: Patients with transitional cell carcinoma who are selected for BCG treatment should preferably be positively immunoreactive for p63, but negative for both p53 and her2/neu. These patients were less susceptible to recurrence and/or progression after BCG adjuvant therapy. Further studies are needed to investigate the relationship between these three markers and treatment with anti-her2/neu therapies.