Ashwini Esnakula

Strong association of fascin expression with triple negative breast cancer and basal-like phenotype in African-American women

Background Fascin, an actin bundling protein, plays a critical role in cell motility due to formation of actin rich protrusions called filopodia, important in cell migration, invasion and metastatic spread. Fascin overexpression has been associated with epithelial to mesenchymal transition and correlates with progression and unfavourable prognosis in breast carcinoma. Objective To evaluate fascin expression by immunohistochemistry and correlate the expression pattern with clinicopathological parameters in breast cancer in African-American (AA) women, in whom triple negative breast cancer (TNBC), an aggressive subtype, is more prevalent. Methods Tissue microarrays were constructed from formalin-fixed, paraffin-embedded blocks of tumour tissue from primary breast carcinomas in 202 AA women. Immunohistochemical detection of fascin was correlated with four major subtypes of breast carcinoma (luminal A, luminal B, human epidermal growth factor receptor 2 and triple negative (TN)) and other clinicopathological factors, including age, grade, tumour size, stage, regional lymph node status and survival. Results We observed a significant association between fascin expression and TN subtype, oestrogen receptor (ER) negativity, progesterone receptor (PR) negativity, Elston–Nottingham (EN) grade 3 and decreased overall survival. There was also a significant association between expression of CK 5/6, a marker of basal-like phenotype, and fascin expression. Conclusion These results suggest that fascin is a marker for TN subtype having a basal-like phenotype and decreased overall survival. Fascin may represent a target for therapy in TNBC in AA women.

Fatal Disseminated Fusarium Infection in a Human Immunodeficiency Virus Positive Patient

Systemic mycotic infections have been increasing in incidence in immunocompromised patients. Although yeasts are most often isolated, opportunistic fungal infections may also be caused by filamentous fungi, including Aspergillus and Fusarium. Like Aspergillus, Fusarium is angioinvasive with an ability to disseminate widely. Disseminated fusariosis is most commonly linked to prolonged neutropenia. Disseminated infections due to Fusarium are rare in Human Immunodeficiency Virus (HIV) positive patients but have been reported in HIV positive patients with neutropenia and lymphoma. We describe an HIV positive patient without neutropenia, skin lesions, or concomitant malignancy, who developed fatal disseminated infection with possible endocarditis due to Fusarium solani. Early identification of Fusarium is important because of its high level of resistance to several antifungal drugs, with response often requiring combination therapy.

Loss of PTEN in High Grade Advanced Stage Triple Negative Breast Ductal Cancers in African American Women

INTRODUCTION PTEN is a tumor suppressor gene that inhibits cell proliferation by inhibiting the phosphoinositide 3-kinase (PI3 K) signaling pathway. The significance of PTEN mutations resulting in variable PTEN expression and their impact on prognosis of breast cancer is not well established. The objective of our study was to correlate the immunohistochemical expression of PTEN in the four major subtypes of breast carcinoma (Luminal A, Luminal B, HER2 positive, and Triple Negative) in a population of 202 African-American (AA) females with other clinicopathological factors. MATERIALS AND METHODS Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 African-American females. Five micrometer sections were stained with a mouse monoclonal antibody against PTEN. The sections were evaluated for the intensity of cytoplasmic and nuclear reactivity. Bivariate analysis was done via χ2 analysis and survivability data was calculated via the generation of Kaplan-Meier curves (SPSS v19). RESULTS Loss of PTEN expression was associated with ER negative (p = 0.021), PR negative (p = 0.024) and triple negative (p = 0.0024) breast ductal cancers. It was marginally associated with distant metastasis (p = 0.074). There was no association between PTEN loss and recurrence-free survival or overall survival. CONCLUSION In our study, a statistically significant association between PTEN loss and the triple negative breast cancers (TNBC) was found in AA women. PTEN inhibits PI3 K resulting in decreased activation of downstream effector, mammalian target of rapamycin (mTOR). Loss of PTEN results in cell proliferation through activation of mTOR. Targeted therapy with mTOR inhibitors might be useful in the treatment of TNBC.

Scrotal mass and unilateral lung masses with pleural effusion mimicking metastatic testicular malignancy: an unusual presentation of sarcoidosis

Involvement of the genitourinary tract by sarcoidosis may present with a scrotal mass, mimicking infection or malignancy. Sarcoidosis is a systemic granulomatous disease that affects patients of both sexes worldwide. Sarcoidosis of the genitourinary tract is rare. We describe a case of a 33-year-old African–American man who presents with a scrotal mass, mediastinal mass, unilateral lung masses and pleural effusion mimicking testicular malignancy with pulmonary metastases. The histopathological examination of the right testis and lung biopsy revealed granulomatous inflammation consistent with sarcoidosis. Genitourinary sarcoidosis must be a diagnostic consideration, especially in an African-American patient with a scrotal mass. There is a possible association between sarcoidosis and testicular malignancy; hence, underlying malignancy should always be ruled out. Serum tumour markers, ACE, a biopsy of the accessible tissue and intraoperative frozen section analysis aid in establishing the diagnosis of sarcoidosis and leading to appropriate management.

Angiolipoma: rare cause of adult ileoileal intussusception.

Intussusception in adults is rare and more common in the paediatric population. Clinically, most adult patients have chronic non-specific symptoms due to partial obstruction. In contrast, most paediatric patients present with the classic triad of abdominal pain, vomiting and blood in stool. Adult intussusception is commonly associated with an organic aetiology, most likely a benign or malignant neoplasm as a lead point of intussusception. We describe a case of a 29-year-old woman with subacute presentation due to ileoileal intussusception secondary to a polypoid submucosal angiolipoma. Angiolipoma is a benign lesion composed of mature adipose tissue and thin-walled capillaries. The presence of thin-walled vessels differentiates it from a lipoma. Angiolipomas of the small intestine are extremely rare with very few reported cases. This case not only demonstrates an unusual benign lesion as a cause of intussusception, but also illustrates an atypical clinical presentation in adults with intussusception.

Sepsis caused by Mycobacterium terrae complex in a patient with sickle cell disease

Infections are a significant cause of morbidity and mortality in patients with sickle cell disease. Loss of splenic function in these patients makes them highly susceptible to some bacterial infections. Non-tuberculous mycobacterial infections in patients with sickle cell disease are extremely rare and only two cases have been reported previously. We describe a case of sepsis caused by non-tuberculous mycobacterium, Mycobacterium terrae complex in a patient with febrile sickle cell disease. M terrae complex is a rare clinical pathogen and this is the first reported case of sepsis secondary to this organism in a patient with sickle cell disease. The patient responded to imipenem and amikacin therapy.

Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men

Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa.

Abstract 1699: Breast cancer protein markers in African Americans

The purpose of this study is to characterize protein markers in African American breast tumors that correspond to different tumor subtypes, recurrence, and survival. Tissue microarrays (TMA) have been used because they have the advantage of analyzing numerous samples on a single slide and can be used in clinical pathology laboratories. Protein markers that have been used are estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), cyclin A2, cytokeratin 5, vimentin, Bcl2, and Ki67. TMA have been prepared and stained for proteins that will distinguish 5 tumor subtypes: luminal A (ER+ and/or PR+ Her2-); luminal B (ER+ and/or PR+ Her2- Cyclin A2+ and/or Ki67+); luminal B Her2+ (ER+ and/or PR+ Her2+); Her2+ (ER- PR- Her2+), and triple negative (ER- PR- Her2-). These subtypes are known to be associated with different relapse-free survival and overall survival. Luminal B tumors have the same ER+PR+HER2- profile as luminal A tumors; however, luminal B tumors have a poor prognosis, whereas luminal A tumors have the best prognosis of all 5 subtypes. Luminal B tumors can be distinguished from luminal A tumors by staining for cell cycle proteins Cyclin A2 or Ki67, which promote cell proliferation. Cyclin A2 was more frequently expressed than Ki67 in tumors with poor prognosis such as luminal B (ER+PR+HER-) and ER-PR-HER2- (triple negative) tumors. Therefore, Cyclin A2+ may better serve to identify luminal B and triple negative tumors with a poor prognosis and thus aid physicians in treatment decisions. The RASSF1A protein has been reported to inhibit the transcription of Cyclin A2. Methylation of the RASSF1A promoter is expected to decrease RASSF1A transcription and thereby increase Cyclin A2 transcription and protein levels. Significantly increased levels of RASSF1A methylation have been observed in this laboratory with AA ER-PR-HER- breast cancer patients compared to mammoplasty samples. Thus, increased Cyclin A2 protein staining correlated with increased RASSF1A methylation. This is one molecular explanation for elevated cyclin A2 protein levels in triple negative tumors. Discovery of molecular markers and subtypes that are most prevalent in African Americans could lead to a better treatment, targets for therapy, and understanding of the factors contributing to higher mortality in this group compared to other groups. 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 1699. doi:1538-7445.AM2012-1699

Abstract 692: Prognostic indicators associated with breast cancer molecular subtypes in African-American women

Background: Overexpression of Fascin, Endoglin (CD105), and Beta-Catenin has been found to be associated with unfavorable prognosis and progression in hormone-receptor negative breast carcinomas. Specifically, fascin promotes cell motility, while Beta-catenin is involved in cancer invasion, cellular transformation, and metastasis. CD105 is selectively upregulated in small, immature tumor vessels in malignant tumors. The objective of this study was to correlate fascin, CD105, and Beta-Catenin protein expression with clinicopathological factors including age, grade, tumor size, stage, regional node status, survival, and with the four major molecular breast cancer subtypes (luminal A, luminal B, HER2 positive, and Triple Negative [TN]). Methods: Tissue microarrays (TMAs) were constructed from optimally-fixed formalin-fixed, paraffin-embedded tumor blocks from primary breast carcinomas in 203 African-American females. Sections were stained with antitibodies against fascin, CD105, and beta-catenin. The sections were evaluated for the intensity of reactivity (0-3) and the percentage of reactive cells. Cases were categorized as having negative/weak (score 10) fascin expression, negative (score=0) or positive (score>0) CD105 (in tumor cells only) and beta-catenin (cytoplasmic and nuclear) expression. Bivariate analysis was done via χ 2 analysis and survivability data was calculated via the generation of Kaplan-Meier curves (SPSS v19). Statistical significance was assumed if 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 692. doi:1538-7445.AM2012-692