Researchers
Shahidul Islam

Shahidul Islam

MD, PhD, FRCPC, FCAP

Clinician Investigator, Cancer Research

Ottawa Hospital Research Institute

Contact

sislam@ottawahospital.on.ca

613-737-8899, 78297

Office Address: Department of Pathology and Laboratory Medicine The University of Ottawa 501 Smyth Road, Ottawa, ON K1H 8L6 Telephone: 613-737-8899 ext. 78297 Fax: 613-737-8853 Email: sislam@ottawahospital.on.ca

ORCID 0009-0002-8174-3887

Bio

EXECUTIVE SUMMARY:
Dr. Islam's illustrious career in pathology and healthcare spans over 20 years, with a current position as Associate Professor in the Faculty of Medicine at the University of Ottawa. His impact is felt nationally and internationally through his exceptional contributions to clinical practice, teaching, and research.

NATIONAL AND INTERNATIONAL IMPACT:
Dr. Islam's influence in pathology extends beyond the borders of Canada, making him a distinguished figure on both national and international fronts. His leadership roles and contributions to various committees have significantly shaped the field of Cytopathology at the national level.

NATIONAL LEVEL:At the national level, Dr. Islam has been instrumental in the establishment and advancement of the "Area of Focus Competence (AFC) in Cytopathology" diploma program at the Royal College of Physicians and Surgeons of Canada (RCPSC). His role as the Chair of the AFC Cytopathology Specialty Committee solidifies his position as a national leader. His participation in the CanMEDS 2024 Working Group reflects his influence in broadening the definition of crucial roles in healthcare, impacting future generations of physicians.Dr. Islam's impact extends to quality improvement, where he chaired the Cytopathology Scientific Committee at the Institute of Quality Management in Healthcare (IQMH), contributing to the development of "Best Practice Recommendation Guidelines for Gynecologic and Non-Gynecologic Cytopathology." His involvement in the National meeting of Specialty Chairs at RCPSC demonstrates his commitment to excellence across diverse medical disciplines.His commitment to quality assessment is evident through his roles as an Assessor for Pathology by the College of Physicians and Surgeons of Ontario (CPSO) and IQMH, actively contributing to the improvement of healthcare services and standards.Locally, Dr. Islam has significantly impacted diagnostic oncology at The Ottawa Hospital, holding key positions such as Director of Cytopathology and Deputy Head and Site-Chief for anatomical pathology. His leadership roles emphasize the expansion of clinical services and the enhancement of patient care quality.

INTERNATIONAL LEVEL:On the international stage, Dr. Islam's impact is profound. His active participation in 53 prestigious international events, including renowned congresses and conferences, showcases his commitment to advancing knowledge globally. Invitations to speak at international conferences highlight his esteemed status and the demand for his insights.Dr. Islam's contributions to academic literature, including peer-reviewed publications in prestigious journals and authorship of 43 chapters on PathologyOutlines.com, solidify his reputation as a distinguished authority in Pathology and Laboratory Medicine globally.His recognition as a podcast guest on the International Society of Gynecological Pathologists' (ISGyP) LiVE series reflects his commitment to innovative discussions and knowledge dissemination. Invitations as an Expert External Assessor for the Kingdom of Saudi Arabia's Anatomical Pathology Program and engagements with the Pathology Society of Saudi Arabia underscore his international impact.

EDUCATION AND RESEARCH CONTRIBUTIONS:
Dr. Islam's dedication to education is exemplified by his decade-long service as the Residency Program Director for Anatomical Pathology at the University of Ottawa. As a Clinician Investigator at the Ottawa Hospital Research Institute (OHRI), his research activities contribute to the advancement of pathology knowledge.

TEACHING:
Dr. Islam's impact as an educator is profound, extending beyond clinical and research contributions. As the Residency Program Director for Anatomical Pathology at the University of Ottawa, he has played a pivotal role in shaping a supportive educational environment. His national contributions to education include active involvement in developing Competence by Design (CBD) documents for residency training.Internationally, Dr. Islam's commitment to education knows no bounds. His mentorship of international fellows and advocacy for International Medical Graduates (IMGs) integration in Canada demonstrates his dedication to fostering diversity within the healthcare workforce.As the Program Director in Anatomical Pathology, Dr. Islam's influence on resident physicians is evident in their success, with many pursuing specialized training and achieving academic promotions. His commitment to research and teaching excellence is reflected in his mentorship of residents and active involvement in clinical trials.In conclusion, Dr. Islam's impact in clinical practice, teaching, and research transcends national and international boundaries. His leadership, expertise, and commitment to excellence have left an indelible mark on the healthcare community, solidifying his position as a prominent figure in the field of pathology and healthcare worldwide.

Research Goals and Interests

Clinical Interest:

Breast and Gynecologic Oncologic Surgical Pathology
Cytopathology


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.
CLINICAL TRIALS:

1. Tomosynthesis Mammographic Imaging Screening Trial Study ID TEMIST, OHS–REB #20170652–01H, Funding source ECOG–ACRIN Sponsor: Canadian Cancer Trials Group (see CCTG)

Role: Surgical pathology review of cases for the study

The purpose of this study is to investigate whether a new type of x-ray breast imaging system called breast tomosynthesis is as good, or better, and finding breast cancer as digital mammography which is our current standard technology to screen for cancer.

2. Triple Negative Breast Cancer Markers in Liquid Biopsies using Artificial Intelligence Study ID TRICIA, OCREB #1934, Sponsored to his General Hospital

Role: Surgical pathology review of cases for the study

Triple negative breast cancer (TNBC), is named as such because these tumors do not express hormone receptors and HER-2 receptor, and therefore the usual approved therapies that target these receptors are not effective in treating this type of cancer. Therefore, chemotherapy is considered the best available treatment for TNBC, and it can be given prior to surgery to reduce the tumor size. However, not all patients will have their tumors disappear with chemotherapy and in these patients, the tumor will be found by the surgeon at the time of surgery. A recent clinical trial reported that additional chemotherapy with a drug called Capecitabine given after surgery, can decrease the cancer of the tumor coming back in a subgroup of these patients. As cells grow and divide deoxyribonucleic acids (DNA) that are normally located inside the cell can sometimes get released into the bloodstream. Small pieces of DNA released by dividing cells have long been known to be present in the blood of patients with a variety of medical conditions; the selected DNA is also called cell free-DNA (cfDNA). In recent years, scientists have discovered that they can detect cancer by analyzing cfDNA from tumor cells using special blood tests (sometimes referred to as liquid biopsies). Cell free-DNA (cfDNA) may be used to detect early signs of cancer. In addition to cfDNA, blood contains small microscopic vesicles that can contain tumor DNA as well as other markers such as protein ribonucleic acid (RNA). Analysis of these vesicles can result in the identification of markers to detect cancer using a blood test. The purpose of the study is to better understand which patients will benefit from further chemotherapy following surgery as well as tumor response to chemotherapy in TNBC. The sponsor will collect plasma samples, call liquid biopsies and any leftover tumor sample available in the pathology department. They will perform special lab test on the samples and then use specialized computer programming termed artificial intelligence to look at the results. Artificial intelligence is based on the idea of using computer programs to find the best parameters to define data.

3. A Phase II Window of Opportunity Trial of PRMT5 Inhibitor, GSK3326595, in Early Stage Breast Cancer (OTT-19-06) ClinicalTrials.gov Identifier: NCT04676516

Role: Surgical pathology review of cases for the study

This is a phase II, randomized, open label, multi-center, parallel design, window of opportunity trial in up to 60 patients with early stage Hormone Receptor (HR) positive breast cancer evaluating GSK3326595. In a 2:1 randomization, patients will receive GSK3326595:no treatment for 15 +/- 3 days prior to breast surgery. There is no placebo in this trial. Primary Outcome Measures: 1. Complete cell cycle arrest (CCCA) [ Time Frame: 2 years ] The primary outcome is the proportion of patients who achieve a Complete Cell Cycle Arrest (CCCA), defined as a reduction in the proportion of Ki67 positively staining cells to ≤ 2.7%.

4. TAILOR RT: A Randomized Trial of Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer, ClinicalTrials.gov Identifier: NCT03488693

Role: Surgical pathology review of cases for the study

Women with node positive breast cancer normally will receive endocrine therapy and some may receive chemotherapy to help prevent the cancer from coming back. Many women will also receive radiotherapy to the whole breast/chest area and the surrounding lymph glands (called regional radiotherapy). No one really knows whether patients with low risk breast cancer need to receive regional radiotherapy. Some women may be getting regional radiotherapy who do not need it. These women may be exposed to the side effects of their treatment without benefit. Primary Outcome Measures: 1. compare the breast cancer recurrence-free interval (BCRFI) between patients that received regional RT or not [ Time Frame: 9.5 years]

GRANTS:

1. PALM, Pathology and Laboratory Medicine Funding, The Department of Pathology and Laboratory Medicine, The Ottawa Hospital, The University of Ottawa, ON. Molecular characterization of atypical spindle cell lesions on endometrial biopsy specimens; $9000. (2013-2014)

2. PALM, Pathology and Laboratory Medicine Funding, The Department of Pathology and Laboratory Medicine, The Ottawa Hospital, The University of Ottawa, ON. Cadherin-Catenin Expression Profile in Ovarian Carcinomas by Tissue Microarrays (TMA) with Clinicopathologic Correlation; $15, 000. (2010-2011)

3. PALM, Pathology and Laboratory Medicine Funding, The Department of Pathology and Laboratory Medicine, The Ottawa Hospital, The University of Ottawa, ON. Cadherin-Catenin Expression Profile in Primary Invasive Breast Carcinomas by Tissue Microarrays (TMA) with Clinicopathologic Correlation; $15, 000. (2007-2008)

4. Cancer Research Society and Canadian Institute of Health Research, The Role of BRCA1 in DNA Damage and Repair in Sporadic Epithelial Ovarian Cancer- collaborator with the Division of Gynaecologic Oncology, The Ottawa Hospital. (2007-2008)

5. Anatomic Pathology Divisional AFP Reallocation Committee, Department of Pathology and Laboratory Medicine, The University of Ottawa, The Ottawa Hospital, Ottawa, ON. The Role of Gene Expression Profile to Characterize Thyroid Neoplasm; $20,000. (2006-2007)

6. Anatomic Pathology Divisional AFP Reallocation Committee, Department of Pathology and Laboratory Medicine, The University of Ottawa, The Ottawa Hospital, Ottawa, ON. Cadherin Expression Profile in Urinary Bladder and Prostate Carcinomas and its Role in Diagnosis and Prognosis; $20,000. (2006-2007)

7. Eleanor Wood-Prince Grants Initiative, a project of the Woman’s Board of Northwestern Memorial Hospital, Chicago, Illinois, USA. The Role of N-Cadherin in Ovarian Cancer and its Correlation with Clinicopathologic Characteristics; $50,000 US. (2004)

8. Travel grant from the College of American Pathologists for the American Society of Investigative Pathology, October 1999, NIH, Bethesda, Maryland; $2000 US. (1999)

9. Training and Travel grant from The American Association for Cancer to participate in the Histopathobiology of Neoplasia Workshop, July 1995 Keystone Conference Center, Keystone, Colorado; $1500 US. (1995)

10. Doctoral research was funded by grants from National Institutes of Health (NIH), the American Cancer Society, the American Heart Association, Ohio Board of Regents, and the U.S. Department of Defence. These grants were awarded to Dr. Islam’s mentors Dr. Margaret J. Wheelock and Dr. Keith R. Johnson who are two lead scientists in the field of Cadherin. (1993-1998)

11. While at the University of Toledo, Department of Biology, Dr. Islam was instrumental in research for his mentors Dr. Margaret J. Wheelock’s National Institutes of Health Grants R01GM051188-03, R01GM051188-04, and 2R01GM051188-05, R01GM051188-06, titled Aspects of Cadherin / Catenin Complexes. This grant was awarded for fiscal years 1996,1997, 1998 and 1999. The 1998 grant alone was for $262,030. (1993-1998)

12. The American Heart Association also provided funds to Dr. Wheelock and Dr. Johnson that played a direct role in Dr. Islam’s PhD research. Every year the Ohio Board of Regents provides research funds for innovative projects that heighten the prestige and importance of Ohio institutions, including Dr. Islam’s research in cell and molecular biology. The U.S. Department of Defence also provided funds for my PhD studies to advance the field of cell and molecular biology. (1993-1998)

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