Tawfiqul Bhuiya

Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes

Background:Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early.Methods:Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass.Results:Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P<0.05), while a six miRNA profile subset distinguished presurgical plasma from benign and ovarian cancer patients. There were also significant differences in miRNA profiles in presurgical plasma from women diagnosed with ovarian cancer who had short overall survival when compared to women with long overall survival (P<0.05).Conclusion:Our preliminary data support the utility of circulating plasma miRNAs to distinguish women with ovarian cancer from those with a benign mass and identify women likely to benefit from currently available treatment for serous epithelial ovarian cancer from those who may not.

Utility of telepathology as a consultation tool between an off-site surgical pathology suite and affiliated hospitals in the frozen section diagnosis of lung neoplasms

Background: Increasingly, as in our institution, operating rooms are located in hospitals and the pathology suite is located at a distant location because of off-site consolidation of pathology services. Telepathology is a technology which bridges the gap between pathologists and offers a means to obtain a consultation remotely. We aimed to evaluate the utility of telepathology as a means to assist the pathologist at the time of intraoperative consultation of lung nodules when a subspecialty pathologist is not available to directly review the slide. Methods: Cases of lung nodules suspicious for a neoplasm were included. Frozen sections were prepared in the usual manner. The pathologists on the intraoperative consultation service at two of our system hospitals notified the thoracic pathologist of each case after rendering a preliminary diagnosis. The consultation was performed utilizing a Nikon™ Digital Sight camera and web-based Remote Medical Technologies™ software with live video streaming directed by the host pathologist. The thoracic pathologist rendered a diagnosis without knowledge of the preliminary interpretation then discussed the interpretation with the frozen section pathologist. The interpretations were compared with the final diagnosis rendered after sign-out. Results: One hundred and three consecutive cases were included. The frozen section pathologist and a thoracic pathologist had concordant diagnoses in 93 cases (90.2%), discordant diagnoses in nine cases (8.7%), and one case in which both deferred. There was an agreement between the thoracic pathologist′s diagnosis and the final diagnosis in 98% of total cases including 8/9 (88.9%) of the total discordant cases. In two cases, if the thoracic pathologist had not been consulted, the patient would have been undertreated. Conclusions: We have shown that telepathology is an excellent consultation tool in the frozen section diagnosis of lung nodules.

Aberrant Expression of Napsin A in Breast Carcinoma With Apocrine Features

An incidental finding of napsin A–positive breast carcinoma with apocrine features during workup for metastatic cancer in an axillary lymph node led to our investigation of the incidence of napsin A expression in breast carcinomas, focusing on those with apocrine features. We included 97 cases of breast carcinomas and performed immunohistochemistry with napsin A, GATA-3, thyroid transcription factor-1, and GCDFP-15. There was a statistically significant difference between apocrine and nonapocrine cases with respect to polyclonal napsin A H-scores (P < .00152), monoclonal napsin A H-scores (P < .00631), GATA-3 H-scores (P < .00029), and GCDFP-15 H-scores (P < .00251). Of the 49 cases of apocrine carcinoma, monoclonal napsin A antibody was positive in 66.7% of cases, including in 7 (14.6%) that showed 3+ staining. The majority of nonapocrine cases were negative (62.5%) or weakly (1+) positive (29.2%), with none exhibiting 3+ strength. It is important for pathologists to be aware that breast carcinomas with apocrine features can express napsin A.

Periductal Stromal Sarcoma of the Breast With Liposarcomatous Differentiation A Case Report With 10-Year Follow-up and Literature Review

A biphasic tumor with features of benign ductal elements and a malignant stromal component that lacks the architecture of a phylloides tumor represents a diagnostic challenge. A 35-year-old woman presented with a painful mass located in the upper inner quadrant of the right breast. A biopsy revealed histologically that the tumor had a multinodular architecture with malignant spindle cells forming cuffs around multiple open benign ducts. No leaf-like architecture was present. In addition, liposarcomatous differentiation was seen in focal areas. Immunohistochemical staining showed positive for CD34, vimentin and CDK4, and negative for ER, PR, Her2/neu, CD10, CD117, p63, bcl-2, cytokeratin, and MDM2. A diagnosis of periductal stromal sarcoma with liposarcomatous differentiation was established. Following excision with mastectomy and adjuvant chemotherapy, the patient was disease-free for 10 years. To our knowledge, this is the first case report of periductal stromal sarcoma showing liposarcomatous differentiation.

Abstract P2-07-09: Integrative analysis of miRNA and mRNA expression in metastatic versus non-metastatic triple negative breast cancer

Background: Triple Negative Breast Cancer (TNBC) is a subset of breast cancer that is difficult to treat clinically and is characterized by being estrogen receptor (ER) negative, progesterone receptor (PR) negative, and does not overexpress human epidermal growth factor receptor 2 (HER2). Patients with TNBC tend to have a worse prognosis than other breast cancer subtypes. Methods: We obtained fifteen TNBC sample FFPE tissue blocks with corresponding plasma samples. All samples were from primary tumors; seven samples having metastasized, four samples that had not metastasized and four samples with unknown metastatic status. The total RNA was isolated from FFPE blocks using the RecoverAll Total Nucleic Acid Isolation Protocol. miRNA from plasma was isolated using Ambion9s mirVANA kit. The plasma and tissue miRNAs were evaluated using the QuantStudio qPCR platform, capturing ˜750 miRNAs. The mRNA was processed using the TruSeq RNA Access kit and sequenced on the Illumina NextSeq platform. Analysis of the miRNA and mRNA individually was performed using limma and DESeq2 packages, respectively. Gene enrichment analysis of the mRNA expression was done using the GAGE package on KEGG pathways while the integrative analysis was done with sparse Canonical Correlation Analysis (sCCA) using the PMA pacakge. Results: Analysis of plasma miRNA had four miRNAs with a significant difference in raw p-value (p Conclusions: One of the circulating plasma miRNAs, miR483-3p, has been found to promote tumorigenesis, while miR581f and miR766 have not been reported in cancer to date. Further investigation into these miRNA could provide a feasible biomarker. The downregulation of immune pathways observed within the metastatic TNBC subjects implies immune evasion is of particular importance for metastasis and a targeted immunotherapy may be a viable treatment option. The integrative analysis of the miRNA and mRNA showed an enrichment in pathways previously linked to increased proliferation and chemoresistance, with an increased signal compared to either miRNA or mRNA alone. Citation Format: Shih AJ, Korsunsky I, Guttadauria B, Bhuiya T, Liew A, Khalili H, Gregersen PK, Lee AT. Integrative analysis of miRNA and mRNA expression in metastatic versus non-metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-07-09.

Two microRNA signatures for malignancy and immune infiltration predict overall survival in advanced epithelial ovarian cancer

MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy-related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune-related functions, was strongly correlated with imputed intratumoral immune infiltrates of T cells, natural killer cells, cytotoxic lymphocytes, and macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publicly available The Cancer Genome Atlas data set. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival.

Abstract 4150: Circulating microRNA patterns in ovarian cancer increased expression with surgical intervention and chemotherapy: Stable high presurgical “survival pattern” (SP) miRNA expression may reflect intrinsic ability for recognition and elimination of malignancy

Background: Epithelial ovarian cancer accounts for 90% of all cases of malignant tumors of the ovaries, the majority of patients are diagnosed at stage III disease with 70% of them succumbing to their disease within 5 years. Objectives: We addressed 3 questions 1) are there patterns in the pre-surgical miRNA profiles between survivors of stage III ovarian cancer and patients who do not survive the disease “surviving pattern” (SP) 2) are there changes in the miRNA profiles that occur during or after chemotherapy that convert patients into SP. 3) Do patients with benign ovarian masses have the SP? Methods: Between 2004 and 2011 we investigated in patterns of circulating miRNAs collected before, after surgery, during and after chemotherapy in patients presenting for surgery for ovarian masses. We also collected blood at ovarian cancer relapse and tumor and benign ovary (if available) for miRNA analysis. Raw Ct values obtained from Taqman and software Data Assist. Data were processed via programming language R. Raw data were normalized using the least variable miRNA from dataset. Differential expression was studied using the R/Bioconductor package “limma” using moderated t-statistic allowing both 2 sample comparison and multiple sample comparison. Only results with a p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4150. doi:1538-7445.AM2012-4150