Cadherin Expression Profile in Prostate Carcinomas and its Role in Diagnosis and Prognosis The current study explored the differential expression of E-cadherin, N-cadherin, cadherin-11 and β -catenin in PAC with different Gleason scores
From this pilot study we conclude that prostatic adenocarcinoma with higher Gleason scores is likely to be associated with gradual loss of membranous E-cadherin and β-catenin expression with a shift in cellular localization of β-catenin from membranous to perinuclear cytoplasmic expression. In contrast to earlier studies, we failed to detect N-cadherin expression in any of the 15 adenocarcinomas.  In addition, we failed to detect mesenchymal cadherin-11 expression in adenocarcinoma cells.    ·    Gene Expression Profile in Thyroid Neoplasm The study began with identifying the molecular markers that could help in the differential diagnosis of follicular adenoma vs. follicular carcinoma of the thyroid.  In this study we examined the differential cellular localization of E-cadherin, and N-cadherin, along with β-catenin in thyroid follicular adenoma, follicular carcinoma, and papillary carcinoma. The study concludes that 1) localization profiles of cadherins and β-catenin are different in follicular adenoma, follicular carcinoma, and papillary carcinoma, 2) follicular carcinoma and papillary carcinoma express β-catenin in the cytoplasm of the neoplastic cells, but most of the follicular adenomas show co expression of this marker in the membrane and cytoplasm, 3) N-cadherin is positive in most of the follicular adenomas and carcinomas, but negative in most of the papillary carcinomas.  Thus cadherins and β-catenin localization may help in differentiating follicular adenomas from follicular carcinomas, and follicular carcinomas and adenomas from papillary carcinomas (follicular and encapsulated variant).   ·   

Differential Localization of Cadherin Catenin Complex in Malignant Mesothelioma and Lung: Adenocarcinoma
This study explored the differential expression and cellular localization of cadherins, namely E-cadherin, N-cadherin, and cadherin-11 along with β-catenin in malignant mesothelioma and lung adenocarcinoma.  The study concludes 1) in general, malignant mesotheliomas are positive for N-cadherin and cadherin-11 and they are negative for E-cadherin, 2) adenocarcinomas are generally positive for E-cadherin and are negative for N-cadherin and cadherin-11 and 3) Expression profile of β-catenin is not useful in differentiating adenocarcinoma from malignant mesothelioma.   ·   

Localization of D2-40 and Podoplanin in Lung Adenocarcinoma and Mesothelioma
Diagnostic Utility in discriminating these two Entities The aim of this study is to examine the expression and localization profile of podoplanin and D2-40 in mesotheliomas and adenocarcinomas of the lung and to assess their diagnostic utility as tissue biomarkers.  From this study, we conclude that all most all mesotheliomas express D2-40 and podoplanin; in contrast all most all adenocarcinomas are negative for these antigens.   ·   

Cadherin-Catenin Expression Profile in Primary Invasive Breast Carcinomas by Tissue Micro arrays (TMA) with Clinicopathologic Correlation By constructing tissue microarrays (TMAs)
We investigated the relationship between cadherin and catenin expression and breast cancer. To maximize immunohistochemical resources and minimze tissue use, the tissue microarray technique was employed. The study concludes that E-cadherin and beta-catenin expression are not associated with nodal metastases. While promising, the relationship between N-cadherin expression and nodal metastases should be validated in a larger prospective study.   ·   

Expression Profile of p16 (INK 4a) and MIB1 (Ki-67) in High Grade Squamous Intraepithelial Lesion (HSIL) and Immature Squamous Metaplasia (ISM) of the Uterine Cervix
The purpose of the current study was to examine p16 and MIB1 expression profile and cellular localization in HSIL and ISM of the uterine cervix.  From this study, we conclude that diffuse and strong nuclear and cytoplasmic p16 expression in combination with strong MIB1 nuclear expression in basal, parabasal and intermediate cells favour HSIL over IMS.   ·   

Aberrant Expression of Cadherin And Catenin Proteins In Ovarian Carcinoma
The cadherin and catenin family of proteins help cells bind to and communicate with each other. Aberrant expression of cadherins and catenins in different neoplasms plays an important role in epithelial to mesenchymal transformation, progression and metastasis. However, a comprehensive expression pattern of most cadherins and catenins in ovarian neoplasms and relationship to chemotherapeutic response remains to be studied. Our aim was to correlate protein expression and localization of cadherins and catenins with pertinent clinicopathologic parameters in ovarian neoplasms using tissue microarrays. Expression of E-cadherin, N-cadherin and beta-catenin was first compared in a preliminary cohort of different ovarian neoplasms followed by a larger cohort of only stage III-IV serous ovarian carcinomas. The majority of cases were chemonaive while a small subset received neoadjuvant chemotherapy with carboplatinum and taxol. Conclusion: We found increased membranous E-cadherin and stippled beta catenin protein expression in clear cell carcinomas. Further studies of expression of a comprehensive array of cadherins and catenins in ovarian carcinomas may provide further insight into the pathogenesis of serous neoplasms and may elucidate the predictive potential of some of these proteins in disease recurrence and tumor metastasis.   ·   

Raman spectroscopy and imaging of cancerous tissues
Raman spectroscopy is a powerful analytical technique that offers many advantages, in particular a high specificity that allows precise detection of the physicochemical makeup of Raman-active materials. Raman spectroscopy is based on detecting different inelastic photon scatterings as a result of the interaction between a monochromatic light and Raman-active molecular vibrations. Interpretation of Raman spectra indicates information about chemical composition, molecular bonding, symmetry and structures, as well as other physical parameters. Recent developments in combining Raman spectroscopy with optical microscopy have provided a new non-invasive strategy to study bone diseases and various cancers.[1,2] In this context, this technique has shown a great potential for the in vitro and in vivo investigation of breast and ovarian cancers,[3-5] promising to have an increasingly important role in cancer early detection and diagnosis. Specific Objectives:To apply Raman spectroscopy and imaging to visualise the physicochemical composition of tissues in order to distinguish endometrium that is benign from that with endometrial cancer   Surgical/Cyto-Pathology Projects ·   

Clinical Relevance and Practice Experience of Reporting Atypical Squamous Cells Cannot Exclude High Grade Squamous Intraepithelial Lesion, (ASC-H)
The current study explored the diagnostic parameters and pitfalls in the follow up of 123 cases of PAP smears diagnosed as ASC-H at our institution. The results of this study are in keeping with previous studies that support the notion that the category of ASC-H is an important entity in the 2001 Bethesda System. In addition, the study concludes that 59.4% of the cases that were diagnosed cytologically as ASC-H were found to have HSIL on subsequent biopsies. Interestingly, this correlation was stronger in patients below the age of 40 years compared to patients above the age of 40 years (65.1% vs. 47.5%). The cytopathologic feature most strongly associated with HSIL was the presence of coarse chromatin (84%).   ·    Cytohistologic Correlation of Benign Pulmonary Nodules with Radiologic Features The purpose of this study was to evaluate the cytologic features of six cases of biopsy proven benign pulmonary nodules with radiologic and histologic correlation. The study concludes that the cytological features useful in separating benign pulmonary nodules are: cohesive cell clusters, inflammatory and histiocytic cells with giant cells and myxoid stroma in the smear background. The lack of nuclear atypia with bland chromatin profile is useful in diagnosing benign pulmonary nodules.   ·   

Atypical Glandular Cells (AGC) - A Cyto-histological Correlation with Diagnostic Pitfalls: A Five-Year Retrospective Study in a Tertiary Care Hospital
The purpose of this study was to identify features that separate atypical glandular cells associated with glandular neoplasia from its mimickers, both benign and malignant. In the current study, we explore the diagnostic parameters and pitfalls in the follow up of 56 cases of Pap smears diagnosed as atypical glandular cells (AGC) at our institution. The results of this study are in keeping with previous studies, which support the notion that the category of AGC is an important entity in the 2001 Bethesda System. In our study, 10.71 % of the cases that were diagnosed cytologically as AGC were found to have adenocarcinoma on subsequent biopsies. Interestingly, this correlation was stronger in patients above the age of 50 years compared to patients below the age of 50 years (25% vs. 5%). The cytopathologic features most strongly associated with adenocarcinoma were the presence of coarse clumpy nuclear chromatin, cytoplasmic vacuolization and three-dimensional clusters.   ·   

Indeterminate for Neoplasia in the Diagnosis of Thyroid FNAB
Cytohistologic Correlation and Diagnostic Pitfalls-a 5 year Retrospective Study in a Tertiary Care Hospital, Ontario, Canada  This is a study of 5-year look back in a Tertiary Care Facility (the Ottawa Hospital) with cyto-histologic correlation to identify diagnostic pitfalls in the diagnosis of follicular lesions (inconclusive/indeterminate). Follow-up of 205 cases showed follicular Adenoma (FA) in 53 (25.8%), Hurthle cell adenoma (HA) in 19 (9.2%), multi-nodular goitre (MGN) in 95 (46.3%), papillary carcinoma, follicular variant (PTCFV) in 25 (12.2%), thyroiditis (THY) in 8 (3.9%) and follicular carcinoma (FC) in 5 (2.4%) patients. Hard cytologic features that accurately predict FA (48 specimens), FC (4 specimens) and PTCFV (23 specimens) are tight microfollicle formations (defined as acinar structures formed by crowed enlarged nuclei with chromatin clearing and inconspicuous nucleoli) present >60% in the smears and scant to nil colloid.  The most common diagnostic pitfall is follicular cells wrapped up in clotted blood and endothelial cells (MGN, 87 specimens). The study concludes that the hard cytologic features that will increase diagnostic specificity of FN (FA, FC and PTCFV) are tight microfollicle formations present in more than 60% of the smears and scant colloid.   The most common diagnostic pitfall is clotted blood.   ·   

Bronchoalveolar Carcinoma of the Lung- A Cytohisto Correlation with Diagnostic Pitfalls Demonstration of a well-differentiated, localized tumor with lepidic growth pattern suggests a BAC. But well differentiated adenocarcinoma or an adenocarcinoma of mixed subtype with invasive patterns can also give a similar deceiving picture. The rate of concordance of radiologic and cytologic appearance of BAC with the subsequent final histological diagnosis is not well established.  We did a retrospective search of all cases that were diagnosed as 'BAC' following FNAC at the Ottawa Hospital ('00 -'09). All cases had a prior CT scan and needed to have a subsequent wedge resection or lobectomy with evaluations done at our institution. Correlations between radiologic, cytological and subsequent histopathological diagnosis was then evaluated.The study shows that only 35% of lesions appearing as BAC on CT scan are subsequently confirmed by both cytology and histology. A cytologic diagnosis of BAC is inaccurate in >60% of cases.   ·   

Missed  Malignancy on Breast Biopsy Diagnosed as a Papillary Lesion
Papillary lesions are a frequent finding from breast biopsy and include intraductal papillomas, papillary lesions with or without atypia and papillary carcinomas.  It is controversial whether or not to excise benign papillary lesions diagnosed on biopsy because only a fraction of lesions are later found to contain malignancy.  The purpose of this study was to determine the frequency of missed malignancy in papillary breast lesions at our institution and to determine the factors that may have contributed to the missed diagnosis.   Whether or not to excise papillary lesions of the breast continues to be a matter of debate.  We have demonstrated that at our institution that nearly half of the women diagnosed with papillary lesions of the breast who go on to surgical resection, will be found to harbor a malignancy. Radiological findings did not predict the discovery of malignancy at resection.  Our data indicate that the most common cause for this discrepancy is sampling error with the malignancy not being present within the biopsy material.  Due to the high rate of malignancy at resection, our data suggest that women diagnosed with papillary lesions on biopsy should undergo local resection in order to avoid missing a malignancy that may not have been sampled in the biopsy.   ·    Multifocal Flat Epithelial Atypia: Possible Precursor of Breast Carcinoma The biological behaviour and management of flat epithelial atypia in breast is not yet established. Whether or not extensive or multifocal FEA is associated with genetic changes that predispose to more advanced breast lesions has not been extensively studied. The aims of this study were: 1. To characterize the radiological presentation, distribution and clinical outcome of FEA; and 2. Evaluate association of FEA distribution with atypical hyperplasia and in situ or invasive carcinoma. We are the first to report that multifocal or extensive FEA is more frequently associated with atypical hyperplasia, in situ or invasive carcinoma. Therefore focality of FEA must be mentioned in the diagnosis. Further molecular and genetic studies are required to elucidate whether or not multifocal FEA is a premalignant condition.