Publications by authors named "Linda Moreau"

40 Publications

Incidence and Mortality of Prostate Cancer in Canada during 1992-2010.

Curr Oncol 2021 Feb 21;28(1):978-990. Epub 2021 Feb 21.

Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada.

In Canada, prostate cancer is the most common reportable malignancy in men. We assessed the temporal trends of prostate cancer to gain insight into the geographic incidence and mortality trends of this disease. Three independent population-based cancer registries were used to retrospectively analyze demographic data on Canadian men diagnosed with prostate cancer and men who died of prostate cancer between the years of 1992 and 2010. The incidence and mortality rates were calculated at the provincial, city, and forward sortation area (FSA) postal code levels by using population counts that were obtained from the Canadian Census of Population. The Canadian average incidence rate was 113.57 cases per 100,000 males. There has been an overall increasing trend in crude prostate cancer incidence between 1992 and 2010 with three peaks, in 1993, 2001, and 2007. However, age-adjusted incidence rates showed no significant increase over time. The national mortality rate was calculated to be 24.13 deaths per 100,000 males per year. A decrease was noted in crude and age-adjusted mortality rates between 1992 and 2010. Several provinces, cities, and FSAs had higher incidence/mortality rates than the national average. Several of the FSA postal codes with the highest incidence/mortality rates were adjacent to one another. Several Canadian regions of high incidence for prostate cancer have been identified through this study and temporal trends are consistent with those reported in the literature. These results will serve as a foundation for future studies that will seek to identify new regional risk factors and etiologic agents.
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http://dx.doi.org/10.3390/curroncol28010096DOI Listing
February 2021

Epidemiology of invasive ocular surface squamous neoplasia in Canada during 1992-2010.

Br J Ophthalmol 2020 10 16;104(10):1368-1372. Epub 2020 Jan 16.

Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada

Background: Ocular surface squamous neoplasia (OSSN) is the most common non-pigmented ocular surface malignancy. It is classified as invasive OSNN (IOSSN) when the underlying stroma are infiltrated by dysplastic squamous epithelial cells through the basement membrane. Here, we present the descriptive epidemiology and geographical distribution of IOSSN in Canada.

Methods: We determined the incidence and geographical distribution of IOSSN cases diagnosed between 1992 and 2010 using two independent population-based cancer registries: the Canadian Cancer Registry and Le Registre Québécois du Cancer.

Results: The mean annual age-standardised incidence rate (WHO 2000-2025) of IOSSN for 1992-2010 was 0.45 cases per million individuals per year with an average annual percent increase in incidence of 4.5%. IOSSN localisation to the conjunctiva was documented in at least 57% of the reported cases. IOSSN exhibited a male predilection ratio of 3.3:1.0 with a mean age at diagnosis of 69 years. Incidence rates of IOSSN across Canadian provinces and cities showed no significant differences from the crude national average.

Conclusions: Our results, particularly concerning IOSSN patient age and male predilection, corroborate with data reported from the USA. Additional studies are needed to determine whether the observed increase in incidence rate over the study period (1992-2010) is significant.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314650DOI Listing
October 2020

Epidemiology of ophthalmic lymphoma in Canada during 1992-2010.

Br J Ophthalmol 2020 08 13;104(8):1176-1180. Epub 2019 Nov 13.

Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada

Background: Ophthalmic lymphoma (OL) is the most common orbital tumour, particularly in older individuals. Little is known about the epidemiology and geographic distribution of OL in Canada. Descriptive demographic statistics are an important first step in understanding OL burden and are necessary to inform comprehensive national cancer prevention programmes.

Methods: We determined patterns of incidence and geographical distribution of the three major subtypes of OL: extranodal marginal zone B cell lymphoma, follicular lymphoma (FL) and diffuse large B cell lymphoma. Here, we used cases that were diagnosed during 1992-2010 using two independent population-based cancer registries, the Canadian Cancer Registry and Le Registre Québécois du Cancer (LRQC).

Results: The OL mean annual age-standardised incidence rate for 1992-2010 was 0.65 cases per million people per year with an average annual increase in the incidence rate of 4.5% per year. The mean age of diagnosis was 65 years. OL incidence rate was the highest in the cities located along the heavily industrialised Strait of Georgia in British Columbia.

Conclusions: Our data on patient age, sex and temporal trends showed similarities with data reported in the USA and Denmark. Additional studies are needed to determine whether the observed increase in OL incidence is genuine or spurious.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314653DOI Listing
August 2020

Penile Invasive Squamous Cell Carcinoma: Analysis of Incidence, Mortality Trends, and Geographic Distribution in Canada.

J Cutan Med Surg 2020 Mar/Apr;24(2):124-128. Epub 2019 Nov 13.

Division of Dermatology, McGill University, Montreal, QC, Canada.

Background: Penile invasive squamous cell carcinoma (SCC) is a rare disease with several known risk factors. However, few studies have assessed its incidence, mortality, and temporal trends.

Objective: Our objectives are to analyze the epidemiology of penile SCC in Canada and to examine patient distribution with this cancer across Canada in order to elucidate population risk factors.

Methods: Three independent cancer registries were used to retrospectively analyze demographic data from Canadian men diagnosed with penile invasive SCC between 1992 and 2010. The Canadian Census of Population was used to calculate incidence and mortality rates at the province and Forward Sortation Area levels.

Results: The overall age-adjusted incidence rate was 6.08 cases per million males. Four provinces with statistically significantly higher incidence rates were identified. The national crude incidence rates increased linearly between 1992 and 2010, whereas the age-adjusted incidence rates showed no significant increase during this time period. The overall age-adjusted mortality rate was 1.88 deaths per million males per year. The province of Saskatchewan had significantly higher mortality rates. There was no increase in crude or age-adjusted mortality rates between 1992 and 2010. There was a significant positive correlation between incidence rates and obesity, Caucasian ethnicity, and lower socioeconomic status.

Conclusion: This study was able to establish geographic variation for this malignancy at the provincial level. Although there are many established risk factors for penile SCC, our results suggest that the increase in crude incidence rates observed is largely due to the aging population.
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http://dx.doi.org/10.1177/1203475419888869DOI Listing
January 2021

Analysis of incidence, mortality trends, and geographic distribution of breast cancer patients in Canada.

Breast Cancer Res Treat 2019 Dec 4;178(3):683-691. Epub 2019 Sep 4.

Division of Dermatology, McGill University, Rm. E02.6236, 1001 Decarie Blvd, Montréal, QC, H4A 3J1, Canada.

Background/purpose: Breast cancer is the malignancy with the highest incidence rate excluding non-melanoma skin cancers, and the second leading cause of cancer-related deaths among Canadian women. Many modifiable risk factors have been linked to the pathogenesis of this disease. The purpose of this study is to analyze the epidemiology of breast cancer in Canada and to examine its geographic distribution to help identify new risk factors for this disease.

Methods: Three independent population-based cancer registries were used to retrospectively analyze demographic data from Canadian women diagnosed with invasive breast cancer across all provinces and territories between 1992 and 2010. The incidence and mortality rates were assessed at the provincial, city, and forward sortation area (FSA) postal code levels.

Results: The overall age-adjusted incidence rate was 114.4 cases per 100,000 females per year. Six provinces and several groups of FSAs had significantly higher incidence rates. There was a significant increase in incidence and decrease in mortality rates between 1992 and 2010. The overall mortality rate was 31.5 deaths per 100,000 females per year. However, three provinces had significantly higher mortality rates.

Conclusion: By identifying high-incidence areas for breast cancer, our study will help identify patient populations that are at higher risk for this malignancy. It will also act as a foundation for future studies to establish novel risk factors for this disease.
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http://dx.doi.org/10.1007/s10549-019-05418-2DOI Listing
December 2019

Multiple myeloma epidemiology and patient geographic distribution in Canada: A population study.

Cancer 2019 07 5;125(14):2435-2444. Epub 2019 Apr 5.

Division of Dermatology, University of Ottawa, Ottawa, Ontario, Canada.

Background: Multiple myeloma (MM) is a malignancy of mature plasma cells. Environmental risk factors identified for this malignancy, among others, include farming and exposure to pesticides.

Methods: Using 3 independent population-based databases (the Canadian Cancer Registry, le Registre Québécois du Cancer, and Canadian Vital Statistics), this study analyzed patients' clinical characteristics and the incidence, mortality, and geographic distribution of MM cases in Canada during 1992-2015.

Results: In total, ~32,065 patients were identified, and 53.7% were male. The mean age at the time of diagnosis was 70 ± 12.1 years. The average incidence rate in Canada was 54.29 cases per million individuals per year, and linear regression modeling showed a steady rise in the annual rate of 0.96 cases per million individuals per year. At the provincial level, Quebec and Ontario had significantly higher incidence rates than the rest of Canada. An analysis of individual municipalities and postal codes showed lower incidence rates in large metropolitan areas and in high-latitude regions of the country, whereas high incidence rates were observed in smaller municipalities and rural areas. Land use analysis demonstrated increased density of crop farms and agricultural industries in high-incidence areas. A comparison with the available data from 2011-2015 showed several consistent trends at provincial, municipal, and regional levels.

Conclusions: These results provide a comprehensive analysis of the MM burden in Canada. Large metropolitan cities as well as high-latitude regions were associated with lower MM incidence. Higher incidence rates were noted in smaller cities and rural areas and were associated with increased density of agricultural facilities.
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http://dx.doi.org/10.1002/cncr.32128DOI Listing
July 2019

Uveal melanoma incidence trends in Canada: a national comprehensive population-based study.

Br J Ophthalmol 2019 12 28;103(12):1872-1876. Epub 2019 Feb 28.

Division of Dermatology, McGill University Health Centre, Montreal, Québec, Canada

Background: In the developed countries, uveal melanoma is the most common primary intraocular malignancy in adults. Little is known about the epidemiological and geographical distribution of uveal melanoma in Canada.

Methods: To determine the incidence patterns and geographical distribution of uveal melanoma cases in Canada, we conducted the first comprehensive, population-based national study of this malignancy across all Canadian provinces and territories during 1992-2010 years. We examined two independent population-based registries: the Canadian Cancer Registry and Le Registre Québécois du Cancer using corresponding International Classification of Diseases for Oncology-3rd edition codes for all histological subtypes of uveal melanoma.

Results: We report that 2215 patients were diagnosed with uveal melanoma, of which 52.1% were males. The average -annual incidence rate of uveal melanoma in Canada was 3.75 cases per million individuals per year (95% CI 3.60 to 3.91). Overall, we report a steady increase in uveal melanoma incidence with an annual increase of 0.074 cases per million individuals per year. Significant differences in the incidence rates of uveal melanoma between Canadian provinces and territories were noted, where the highest crude incidence was in British Columbia and Saskatchewan with rates of 6.38 and 5.47 cases per million individuals per year, respectively.

Conclusions: This work, for the first time, defines the disease burden of uveal melanoma in Canada and highlights important longitudinal, geographical and spatial differences in the distribution of uveal melanoma in Canada.
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http://dx.doi.org/10.1136/bjophthalmol-2018-312966DOI Listing
December 2019

Analysis of acute myeloid leukemia incidence and geographic distribution in Canada from 1992 to 2010 reveals disease clusters in Sarnia and other industrial US border cities in Ontario.

Cancer 2019 06 27;125(11):1886-1897. Epub 2019 Feb 27.

Division of Dermatology, University of Ottawa, Ottawa, Ontario, Canada.

Background: Several risk factors have been implicated in acute myeloid leukemia (AML) leukemogenesis. However, the epidemiologic distribution and precise triggers for AML in Canada remain poorly understood.

Methods: In this study, demographic data for AML patients in Canada from 1992 to 2010 were analyzed using 3 independent population-based cancer registries. The AML incidence and mortality rates were examined at the levels of province/territory, city, and forward sortation area (FSA) postal code.

Results: In total, 18,085 patients were identified. AML incidence was documented to be 30.61 cases per million individuals per year (95% confidence interval [CI], 30.17-31.06) from 1992 to 2010. Five industrial cities in Ontario were identified where incidence rates were significantly higher than the national average: Sarnia, Sault Ste. Marie, Thunder Bay, St. Catharines, and Hamilton. Analysis at the FSA postal code level identified significant patient clusters of AML in these cities. Specifically, FSA N7V in Sarnia, Ontario had an incidence of 106.81 (95% CI, 70.96-161.86) cases per million individuals per year, which is >3 times higher than the national average. The pollution from local oil refineries and chemical plants in Sarnia may be implicated as a risk factor for AML in that city. Analysis of mortality rates at the province and city levels corroborated the findings from the incidence data.

Conclusion: These results provide a comprehensive analysis of AML burden in Canada and reveal striking geographic case clustering in industrial Ontario cities and potentially implicate exposure to materials/pollution from these plants as an important risk factor for developing AML in Canada.
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http://dx.doi.org/10.1002/cncr.32034DOI Listing
June 2019

A study of meiomitosis and novel pathways of genomic instability in cutaneous T-cell lymphomas (CTCL).

Oncotarget 2018 Dec 28;9(102):37647-37661. Epub 2018 Dec 28.

Division of Dermatology, University of Ottawa, Ottawa, Ontario K1H 8L6, Canada.

Genomic instability is a hallmark of cancer and an enabling factor for genetic alterations that drive cancer development and progression. The clashing of mitosis and aberrantly expressed meiosis machineries, which may contribute to genomic instability, has been coined cancer "meiomitosis". retrotransposition, a process active in germ cells, acts outside of the meiotic machinery to create DNA double strand breaks (DNA DSBs) and has played an important role in the evolution of the human genome. We have previously demonstrated that in CTCL several cancer testis/meiotic genes are expressed. Furthermore, this cancer exhibits extensive and ongoing chromosomal/microsatellite instability. In this study we analyzed immortalized patient-derived cells and primary CTCL patient samples using RT-PCR, western blotting and confocal microscopy and found that proteins critically involved in meiosis and retrotransposition are expressed and are associated with chromosomal instability and DNA DSB formation. Using cell cycle synchronization, we show G1/S phase-transition-specific expression of meiosis proteins. Using the Alu retrotransposition assay, we demonstrate the functional activity of retrotransposon in CTCL. Histone acetyltransferase inhibition results in downregulation of the ectopic germ cell programs and concomitant decrease in DNA DSBs foci formation. Notably, and meiosis genes were expressed across a panel of other solid tumor cell lines. Taken together, our results indicate that malignant cells in culture undergo "cancer meiomitosis" rather than the classic mitosis division. The ectopic expression of meiosis genes and reactivation of may be contributing to genomic instability and represent novel targets for immunotherapy in this and other cancers.
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http://dx.doi.org/10.18632/oncotarget.26479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340880PMC
December 2018

Trends in incidence of cutaneous malignant melanoma in Canada: 1992-2010 versus 2011-2015.

J Am Acad Dermatol 2019 Apr 2;80(4):1157-1159. Epub 2018 Nov 2.

Division of Dermatology, McGill University, Montréal, Québec, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2018.10.055DOI Listing
April 2019

Gene expression profiling and immune cell-type deconvolution highlight robust disease progression and survival markers in multiple cohorts of CTCL patients.

Oncoimmunology 2018;7(8):e1467856. Epub 2018 May 31.

Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada.

CTCL follows different courses depending on the clinical stage at the time of diagnosis. Patients with early stage Mycosis Fungoides (MF) variant of CTCL may experience an indolent course over decades, whereas patients with advanced MF and Sézary Syndrome (SS) disease at diagnosis, often succumb within 5 years. Even within early stage CTCL/MF, a minority of patients will progress to more advanced stages. We recently generated RNA sequencing data on 284 CTCL-relevant genes for 157 patients and identified differentially expressed genes across stages I-IV. In this study, we aim to validate robust molecular markers linked to disease progression and survival. We performed multiple hypothesis testing-corrected analysis of variance (ANOVA) on the expression of individual genes across all CTCL samples and early stage (≤IIA) CTCL/MF patients. We used immune cell-type deconvolution from gene expression data to estimate immune cell populations. Based on the analysis of all CTCL samples, we identified , and as predictors of disease progression and poor survival. Among early stage (≤IIA) CTCL/MF patients, these 3 genes, along with , were valuable to predict disease progression. We validated these 4 genes in 3 independent, external Sézary Syndrome patient cohorts with RNA-Sequencing data. immune cell-type deconvolution revealed that neutrophil infiltration in early stage MF conveyed a higher risk for disease progression. Also, NK cell infiltration in late stage MF/SS correlated with improved survival. and are robust disease progression and decreased survival biomarkers in CTCL.
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http://dx.doi.org/10.1080/2162402X.2018.1467856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136868PMC
May 2018

Cutaneous malignant melanoma incidence and mortality trends in Canada: A comprehensive population-based study.

J Am Acad Dermatol 2019 Feb 6;80(2):448-459. Epub 2018 Aug 6.

Divisions of Dermatology, McGill University, Montréal, Canada. Electronic address:

Background: The incidence of cutaneous malignant melanoma (CMM) is on the rise in many parts of the world. However, there is limited knowledge on the epidemiology of CMM in Canada.

Objective: To conduct a comprehensive population-based study of CMM in Canada.

Methods: We examined patient clinical and pathologic characteristics as well as the incidence and mortality trends of CMM in Canada using 3 independent population-based registries.

Results: In total, 72,565 Canadian patients were given CMM diagnoses during 1992-2010; 47.5% were women. Average age at the time of diagnosis was 56.5 years for women and 60.4 years for men. We report a steady increase in CMM incidence and mortality rates in both sexes. The overall incidence rate of CMM in Canada was 12.29 cases/100,000 person-years. We also report important differences in the incidence and mortality rates between Canadian provinces and territories; the highest incidence of this cancer was documented in Nova Scotia and Prince Edward Island.

Limitations: Data on race, clinical disease stage, and Breslow depth of CMM was not available.

Conclusion: This study, for the first time, defines the disease burden of CMM in Canada and highlights important longitudinal, geographic, and spatial differences in the distribution of CMM in this country.
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http://dx.doi.org/10.1016/j.jaad.2018.07.041DOI Listing
February 2019

Occupational Contact Dermatitis in the Canadian Aircraft Industry.

Dermatitis 2018 May/Jun;29(3):139-150

From the Division of Dermatology, Department of Medicine, McGill University Health Centre, Montreal General Hospital, Québec, Canada.

Background: Aircraft building exposes workers to irritant and sensitizing products.

Objective: The aim of this article was to study occupational dermatoses among aircraft workers over 25 years.

Methods: The files of aerospace workers referred between 1990 and 2015 were extracted from the database of the McGill University Health Centre contact dermatitis clinic. These were subdivided according to demographics, type of work, patch testing results, and final diagnosis.

Results: Of 305 workers, 58% were 40 years or younger; one third were women. Onset of dermatitis varied from 2 months to 25 years, but 120 cases (39%) occurred during the first 3 years. Fifty-one percent of the cases involved assemblers, and 27% were composite material technicians, which were overrepresented as they constitute 10% of the workforce. Of the 305 workers, 152 suffered from allergic contact dermatitis, and 96 had irritant contact dermatitis. Of those with allergic contact dermatitis, 124 reacted to epoxy-based workplace products, but only 48 had positive patch tests to commercially available epoxy allergens.

Conclusion: More than 60% of the cases of epoxy allergy would have been missed without testing with workplace products.
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http://dx.doi.org/10.1097/DER.0000000000000361DOI Listing
October 2018

Occupational allergic contact dermatitis caused by hexahydrophthalic acid diglycidyl ester and anhydride epoxy hardeners.

Contact Dermatitis 2018 Jul 21;79(1):39-40. Epub 2018 Feb 21.

Division of Dermatology, McGill University Health Centre, Montreal, Canada.

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http://dx.doi.org/10.1111/cod.12976DOI Listing
July 2018

Distribution and Clustering of Cutaneous T-Cell Lymphoma (CTCL) Cases in Canada During 1992 to 2010.

J Cutan Med Surg 2018 Mar/Apr;22(2):154-165. Epub 2017 Dec 14.

1 Division of Dermatology, University of Ottawa, Ottawa, Ontario, Canada.

Background: Clustering of patients with cutaneous T-cell lymphoma (CTCL) was reported in several jurisdictions around the world. This rare cancer is known to affect spouses and in some cases multiple members of the same family. These combined results suggest the existence of external disease triggers/promoters. We recently conducted the first comprehensive analysis of CTCL incidence and mortality in Canada, which revealed case clustering in several regions.

Objectives: To extend our previous analysis on CTCL incidence across Canada and to provide all the collected data on CTCL patient incidence in Canada during the period of 1992 to 2010.

Methods: Clinical parameters for patients with CTCL in Canada were analyzed using 2 independent population-based cancer registries: Canadian Cancer Registry and Le Registre Québécois du Cancer. The CTCL incidence rates were examined on different geographical levels, including provinces/territories, cities, and forward sortation areas.

Results: Our findings further corroborate our earlier observations of higher CTCL incidence in Newfoundland and Labrador, maritime provinces (Nova Scotia and New Brunswick), and prairie provinces (Manitoba and Saskatchewan). Also, most cities with high CTCL incidence were located in these provinces. Extensive mapping of high-incidence postal codes supports case clustering in a number of communities that are located in the proximity of industrial centres and seaports.

Conclusions: Detailed analysis of CTCL incidence in Canada is critical to fully understand the burden of this disease in our country, to begin the search for a possible external trigger for this lymphoma, and to reform how health care resources are distributed throughout the country to better serve Canadian patients with CTCL.
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http://dx.doi.org/10.1177/1203475417745825DOI Listing
September 2018

TruSeq-Based Gene Expression Analysis of Formalin-Fixed Paraffin-Embedded (FFPE) Cutaneous T-Cell Lymphoma Samples: Subgroup Analysis Results and Elucidation of Biases from FFPE Sample Processing on the TruSeq Platform.

Front Med (Lausanne) 2017 22;4:153. Epub 2017 Sep 22.

Division of Dermatology, McGill University Health Centre, Montreal, QC, Canada.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of malignancies with courses ranging from indolent to potentially lethal. We recently studied in a 157 patient cohort gene expression profiles generated by the TruSeq targeted RNA gene expression sequencing. We observed that the sequencing library quality and depth from formalin-fixed paraffin-embedded (FFPE) skin samples were significantly lower when biopsies were obtained prior to 2009. We also observed that the fresh CTCL samples clustered together, even though they included stage I-IV disease. In this study, we compared TruSeq gene expression patterns in older (≤2008) vs. more recent (≥2009) FFPE samples to determine whether these clustering analyses and earlier described differentially expressed gene findings are robust when analyzed based on the year of biopsy. We also explored biases found in FFPE samples when subjected to the TruSeq analysis of gene expression. Our results showed that ≤2008 and ≥2009 samples clustered equally well to the full data set and, importantly, both analyses produced nearly identical trends and findings. Specifically, both analyses enriched nearly identical DEGs when comparing benign vs. (1) stage I-IV and (2) stage IV (alone) CTCL samples. Results obtained using either ≤2008 or ≥2009 samples were strongly correlated. Furthermore, by using subgroup analyses, we were able to identify additional novel differentially expressed genes (DEGs), which did not reach statistical significance in the prior full data set analysis. Those included CTCL-upregulated , and and CTCL-downregulated , and genes. With respect to sample biases, no matter if we performed subgroup analyses or full data set analysis, fresh samples tightly clustered together. While principal component analysis revealed that fresh samples were spatially closer together, indicating some preprocessing batch effect, they remained in the proximity to other normal/benign and FFPE CTCL samples and were not clustering as outliers by themselves. Notably, this did not affect the determination of DEGs when analyzing ≥2009 samples (fresh and FFPE biopsies) vs. ≥2009 FFPE samples alone.
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http://dx.doi.org/10.3389/fmed.2017.00153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614967PMC
September 2017

Evaluating Comorbidities, Natural History, and Predictors of Early Resolution in a Cohort of Children With Chronic Urticaria.

JAMA Dermatol 2017 12;153(12):1236-1242

Division of Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Centre, Montreal, Quebec, Canada.

Importance: Chronic urticaria (CU) affects 0.1% to 0.3% of children. Most cases have no identifiable trigger and are classified as chronic spontaneous urticaria (CSU). At least half of patients with CSU may have an autoimmune etiology that can be determined in vitro using the basophil activation test (BAT). While 30% to 55% of CU cases resolve spontaneously within 5 years in adults, the natural history and predictors of resolution in children are not known.

Objective: To assess the comorbidities, natural history of CU, and its subtypes in children and identify predictors of resolution.

Design, Setting, And Participants: We followed a pediatric cohort with chronic urticaria that presented with hives lasting at least 6 weeks between 2013 and 2015 at a single tertiary care referral center.

Exposures: Data were collected on disease activity, comorbidities, physical triggers, BAT results, complete blood cell count, C-reactive protein levels, thyroid-stimulating hormone levels, and thyroid peroxidase antibodies.

Main Outcomes And Measures: We assessed the rate of resolution (defined as absence of hives for at least 1 year with no treatment) and the association with clinical and laboratory markers.

Results: The cohort comprised 139 children younger than 18 years old. Thirty-one patients (20%) had inducible urticaria, most commonly cold induced. Six children had autoimmune comorbidity, such as thyroiditis and type 1 diabetes. Autoimmune disorders (24 patients [17%]) and CU (17 patients [12%]) were common in family members. Positive BAT results (CD63 levels > 1.8%) were found in 58% of patients. Patients with positive BAT results (CD63 level >1.8%) were twice as likely to resolve after 1 year compared with negative BAT results (hazard ratio [HR], 2.33; 95% CI, 1.08-5.05). In contrast, presence of basophils decreased the likelihood of resolution (HR, 0.40; 95% CI, 0.20-0.99). No correlation with age was found. Chronic urticaria resolved in 43 patients, with a rate of resolution of 10.3% per year. Levels of CD63 higher than 1.8% and absence of basophils were associated with earlier disease resolution.

Conclusions And Relevance: Resolution rate in children with CU is low. The presence of certain biomarkers (positive BAT result and basophil count) may help to predict the likelihood of resolution.
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http://dx.doi.org/10.1001/jamadermatol.2017.3182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817447PMC
December 2017

Point-of-care wound visioning technology: Reproducibility and accuracy of a wound measurement app.

PLoS One 2017 17;12(8):e0183139. Epub 2017 Aug 17.

Department of Medicine, Division of Dermatology, McGill University, Montreal, Quebec, Canada.

Background: Current wound assessment practices are lacking on several measures. For example, the most common method for measuring wound size is using a ruler, which has been demonstrated to be crude and inaccurate. An increase in periwound temperature is a classic sign of infection but skin temperature is not always measured during wound assessments. To address this, we have developed a smartphone application that enables non-contact wound surface area and temperature measurements. Here we evaluate the inter-rater reliability and accuracy of this novel point-of-care wound assessment tool.

Methods And Findings: The wounds of 87 patients were measured using the Swift Wound app and a ruler. The skin surface temperature of 37 patients was also measured using an infrared FLIR™ camera integrated with the Swift Wound app and using the clinically accepted reference thermometer Exergen DermaTemp 1001. Accuracy measurements were determined by assessing differences in surface area measurements of 15 plastic wounds between a digital planimeter of known accuracy and the Swift Wound app. To evaluate the impact of training on the reproducibility of the Swift Wound app measurements, three novice raters with no wound care training, measured the length, width and area of 12 plastic model wounds using the app. High inter-rater reliabilities (ICC = 0.97-1.00) and high accuracies were obtained using the Swift Wound app across raters of different levels of training in wound care. The ruler method also yielded reliable wound measurements (ICC = 0.92-0.97), albeit lower than that of the Swift Wound app. Furthermore, there was no statistical difference between the temperature differences measured using the infrared camera and the clinically tested reference thermometer.

Conclusions: The Swift Wound app provides highly reliable and accurate wound measurements. The FLIR™ infrared camera integrated into the Swift Wound app provides skin temperature readings equivalent to the clinically tested reference thermometer. Thus, the Swift Wound app has the advantage of being a non-contact, easy-to-use wound measurement tool that allows clinicians to image, measure, and track wound size and temperature from one visit to the next. In addition, this tool may also be used by patients and their caregivers for home monitoring.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183139PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560698PMC
October 2017

Gene expression analysis in Cutaneous T-Cell Lymphomas (CTCL) highlights disease heterogeneity and potential diagnostic and prognostic indicators.

Oncoimmunology 2017;6(5):e1306618. Epub 2017 Mar 17.

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Cutaneous T-Cell Lymphomas (CTCL) are rare, but potentially devastating malignancies, whose pathogenesis remains poorly elucidated. Unfortunately, currently it is not possible to predict based on the available criteria in which patients the cancer will progress and which patients will experience an indolent disease course. Furthermore, at early stages this malignancy often masquerades as psoriasis, chronic eczema or other benign inflammatory dermatoses. As a result, it takes on average 6 y to diagnose this lymphoma since its initial presentation. In this study, we performed transcription expression profiling using TruSeq targeted RNA gene expression on 181 fresh and formalin-fixed and paraffin-embedded (FFPE) skin samples from CTCL patients and patients affected by benign inflammatory dermatoses that often mimic CTCL clinically and on histology (e.g., psoriasis, chronic eczema, etc.) We also analyzed multiple longitudinal biopsies that were obtained from the same patients over time. Our results underscore significant molecular heterogeneity with respect to gene expression between different patients and even within the same patients over time. Our study also confirmed and genes as being differentially expressed between CTCL and benign skin biopsies. In addition, we found that differential expression for a subset of these markers (e.g., and ) may be useful in prognosticating this disease. This research, combined with other molecular analyses, prepares the foundation for the development of personalized molecular approach toward diagnosis and management of CTCL.
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http://dx.doi.org/10.1080/2162402X.2017.1306618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468001PMC
March 2017

Comprehensive analysis of cutaneous T-cell lymphoma (CTCL) incidence and mortality in Canada reveals changing trends and geographic clustering for this malignancy.

Cancer 2017 Sep 10;123(18):3550-3567. Epub 2017 May 10.

Division of Dermatology, University of Ottawa, Ottawa, Ontario, Canada.

Background: Previous reports of geographic clustering of cutaneous T-cell lymphoma (CTCL) in Texas, Pittsburgh, and Sweden as well as the occurrence of CTCL in married couples and family members raise a possibility of the existence of an external and potentially preventable trigger(s) for this rare skin cancer.

Methods: The authors studied CTCL incidence and mortality in Canada using 3 distinct population-based cancer databases. Data on patients' sex, age at the time of diagnosis, subtype of CTCL malignancy, reporting province, city, and postal code were analyzed. CTCL cases were mapped across Canada using geographic information systems software.

Results: In total, 6685 patients with CTCL were identified in Canada during 1992 through 2010 (CTCL incidence rate, 11.32 cases per million individuals per year), of which 58% were males. The mean age at diagnosis was 59.4 ± 21.5 years. Geographic analysis of patients revealed increased CTCL incidence on the provincial and city levels in several eastern provinces and in Manitoba. An analysis according to postal codes (Forward Sortation Area [FSA]) identified select communities in which several high-incidence FSAs were contiguous or adjacent. Several of these FSAs were located in industrial regions of Canadian cities. Conversely, 3 of 8 low-incidence FSAs were clustered in Ottawa, Ontario, which has very little industrial presence. An analysis of CTCL mortality in Canada corroborated the current incidence findings.

Conclusions: The current results provide a comprehensive analysis of CTCL burden in Canada and highlight several important areas of geographic case clustering. These findings argue that industrial exposures may play an important role in promoting CTCL pathogenesis. Cancer 2017;123:3550-67. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30758DOI Listing
September 2017

Positive CD63 Basophil Activation Tests Are Common in Children with Chronic Spontaneous Urticaria and Linked to High Disease Activity.

Int Arch Allergy Immunol 2016 16;171(2):81-88. Epub 2016 Nov 16.

Division of Dermatology, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.

Background: The basophil activation test (BAT) using CD63 expression is a sensitive and specific tool for the diagnostic workup of autoimmune chronic spontaneous urticaria (CSU). The definition of a positive BAT is directly dependent on the reference range and the cutoff values established in control populations. As of now, the pediatric reference range and cutoff values of the CD63 BAT remain to be established.

Methods: In this study, we analyzed CD63 expression in 80 children (1-17 years old) without chronic urticaria (i.e., controls) and compared the values to those of a pediatric cohort of 105 CSU patients and 23 physical urticaria (PU) patients.

Results: Based on the log-normal distribution of CD63 values in control subjects, the reference range and the cutoff for positive CD63 BAT values was established to be 1.2-1.8% (95% CI) and 1.8%, respectively. Children with CSU showed significantly elevated and significantly increased BAT values compared to healthy controls (Wilcoxon rank test p value <0.001). In contrast, no difference was found between BAT results in controls and PU patients. In pediatric CSU patients, a higher disease activity was associated with higher BAT values.

Conclusions: Our study provides, for the first time, reference and cutoff values for the CD63 BAT in children. Our findings show that positive CD63 BAT are common in children with CSU and linked to a high disease activity.
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http://dx.doi.org/10.1159/000451084DOI Listing
February 2017

Contact Allergy to Polymyxin B Among Patients Referred for Patch Testing.

Dermatitis 2016 May-Jun;27(3):119-22

From the Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada.

Backgound: Polymyxin B is not included in most standard contact allergen series. The aim of this study was to determine the prevalence of contact sensitization to polymyxin B in a population of patients referred for patch testing.

Methods: A retrospective cohort study design was used to collect data on 795 patients referred to the contact dermatitis clinic of the McGill University Health Centre, as well as to the office of one of the authors (L.M.), between March 2014 and November 2015. Patients were patch tested to the North American Contact Dermatitis Group baseline series and polymyxin B sulfate 3% in petrolatum.

Results: Out of 795 tested individuals, 18 were allergic to polymyxin B, for a prevalence of 2.3%. The eruptions affected almost all body parts, but mostly the face. The degree of reaction ranged from 1+ to 2+. Isolated reactions to polymyxin B occurred in 9 (50%) patients, whereas reactions to bacitracin and polymyxin B were seen in the other 9. Only 1 patient reacted to bacitracin, polymyxin B, and neomycin (11.1%). Most reactions (12/18) were from past exposure to polymyxin B.

Conclusions: Allergic reactions to polymyxin B are not rare, and this antibiotic warrants inclusion in the standard patch testing series.
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http://dx.doi.org/10.1097/DER.0000000000000189DOI Listing
February 2018

Demographic patterns of cutaneous T-cell lymphoma incidence in Texas based on two different cancer registries.

Cancer Med 2015 Sep 1;4(9):1440-7. Epub 2015 Jul 1.

Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Cutaneous T-cell lymohomas (CTCLs) are rare, but potentially devastating malignancies, with Mycosis fungoides and Sézary Syndrome being the most common. In our previous study, we identified and described regions of geographic clustering of CTCL cases in Texas by analyzing ~1990 patients using two distinct cancer registries. In the current work, we describe in detail demographic patterns for this malignancy in our study population and apply logistic regression models to analyze the incidence of CTCL by sex, race, age, and clinical stage at the time of diagnosis. Furthermore, using Fisher's exact test, we analyze changes in incidence over time in the identified Houston communities with unusually high CTCL incidence. While CTCL primarily affects Caucasian individuals >55 years old, we confirm that it presents at a younger age and with more advanced disease stages in African-American and Hispanic individuals. Also, we demonstrate a significant increase in CTCL incidence over time in the identified communities. Spring, Katy, and Houston Memorial areas had high baseline rates. Furthermore, a statistically significant disease surge was observed in these areas after ~2005. This report supplements our initial study documenting the existence of geographic clustering of CTCL cases in Texas and in greater detail describes demographic trends for our patient population. The observed surge in CTCL incidence in the three identified communities further argues that this malignancy may be triggered by one or more external etiologic agents.
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http://dx.doi.org/10.1002/cam4.472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567029PMC
September 2015

Ectopic expression of embryonic stem cell and other developmental genes in cutaneous T-cell lymphoma.

Oncoimmunology 2014 Nov 21;3(11):e970025. Epub 2014 Dec 21.

Division of Dermatology; McGill University Health Centre ; Montréal, QC Canada.

Cutaneous T-cell lymphoma (CTCL) is a potentially devastating malignancy. The pathogenesis of this cancer remains poorly elucidated. Previous studies focused on analysis of expression and function of known oncogenes and tumor suppressor genes. However, emerging reports highlight that it is also important to analyze the expression of genes that are ectopically expressed in CTCL (e.g., embryonic stem cell genes (ESC), cancer testis (CT) genes, etc.). Currently, it is not known whether ESC genes are expressed in CTCL. In the current work, we analyze by RT-PCR the expression of 26 ESC genes, many of which are known to regulate pluripotency and promote cancer stem cell-like phenotype, in a historic cohort of 60 patients from Boston and in a panel of 11 patient-derived CTCL cell lines and compare such expression to benign inflammatory dermatoses that often clinically mimic CTCL. Our findings document that many critical ESC genes including () and their upstream and downstream signaling members are expressed in CTCL. Similarly, polycomb repressive complex 2 (PRC2) genes (i.e., ) are also expressed in CTCL lesional skin. Furthermore, select ESC genes () are preferentially expressed in CTCL samples when compared to benign skin biopsies. Our work suggests that ESC genes are ectopically expressed together with CT genes, thymocyte development genes and B cell-specific genes and may be working in concert to promote tumorigenesis. Specifically, while ESC genes may be promoting cancer stem cell-like phenotype, CT genes may be contributing to aneuploidy and genomic instability by producing aberrant chromosomal translocations. Further analysis of ESC expression and function in this cancer will greatly enhance our fundamental understanding of CTCL and will help us identify novel therapeutic targets.
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http://dx.doi.org/10.4161/21624011.2014.970025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368148PMC
November 2014

The Use of Transcriptional Profiling to Improve Personalized Diagnosis and Management of Cutaneous T-cell Lymphoma (CTCL).

Clin Cancer Res 2015 Jun 16;21(12):2820-9. Epub 2015 Mar 16.

Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts.

Purpose: Although many patients with mycosis fungoides presenting with stage I disease enjoy an indolent disease course and normal life expectancy, about 15% to 20% of them progress to higher stages and most ultimately succumb to their disease. Currently, it is not possible to predict which patients will progress and which patients will have a stable disease. Previously, we conducted microarray analyses with RT-PCR validation of gene expression in biopsy specimens from 60 patients with stage I-IV cutaneous T-cell lymphoma (CTCL), identified three distinct clusters based upon transcription profile, and correlated our molecular findings with 6 years of clinical follow-up.

Experimental Design: We test by RT-PCR within our prediction model the expression of about 240 genes that were previously reported to play an important role in CTCL carcinogenesis. We further extend the clinical follow-up of our patients to 11 years. We compare the expression of selected genes between mycosis fungoides/Sézary syndrome and benign inflammatory dermatoses that often mimic this cancer.

Results: Our findings demonstrate that 52 of the about 240 genes can be classified into cluster 1-3 expression patterns and such expression is consistent with their suggested biologic roles. Moreover, we determined that 17 genes (CCL18, CCL26, FYB, T3JAM, MMP12, LEF1, LCK, ITK, GNLY, IL2RA, IL26, IL22, CCR4, GTSF1, SYCP1, STAT5A, and TOX) are able to both identify patients who are at risk of progression and also distinguish mycosis fungoides/Sézary syndrome from benign mimickers.

Conclusions: This study, combined with other gene expression analyses, prepares the foundation for the development of personalized molecular approach toward diagnosis and treatment of CTCL.
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http://dx.doi.org/10.1158/1078-0432.CCR-14-3322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470792PMC
June 2015

Eruptive disseminated pyogenic granulomas following lightning injury.

Dermatology 2015 ;230(3):199-203

Background: Pyogenic granuloma (PG) is a common benign acquired vascular tumor. It classically presents as a solitary friable nodule on the face or distal extremities. Disseminated eruption is rare and can occur spontaneously or secondary to various triggers, including burn injury. To date, the literature reports only 13 cases of eruptive PGs following burn injury, most from exposure to boiling milk or water. We report the first case of disseminated eruptive PGs following a lightning injury.

Case: A 17-year-old previously healthy boy developed second- and third-degree burns following lightning injury. Two weeks later, he developed widespread dark-purple polypoid exophytic tumors ranging from 1 to 10 cm in diameter extending beyond the limits of the initial burn injury. The lesions were friable and often formed erosions and crusts. The patient was otherwise well and laboratory and microbiological investigations were normal. Excisional biopsy of a lesion was diagnostic of PG and the patient was treated with surgical excision of the lesions, without recurrence.

Conclusion: The exact pathogenesis of multiple PGs remains unknown. Several pathogenic mechanisms have been suggested, including production of angiogenic factors that stimulate endothelial proliferation and formation of minute arteriovenous fistulas by trauma.
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http://dx.doi.org/10.1159/000371880DOI Listing
September 2015

Deregulation in STAT signaling is important for cutaneous T-cell lymphoma (CTCL) pathogenesis and cancer progression.

Cell Cycle 2014 ;13(21):3331-5

a Division of Dermatology ; McGill University Health Centre ; Montréal , QC Canada.

Deregulation of STAT signaling has been implicated in the pathogenesis for a variety of cancers, including CTCL. Constitutive activation of STAT5 and STAT3 was observed in early and late stages of CTCL, respectively. In early stages, IL-2, IL-7 and IL-15 signaling via JAK1 and JAK3 kinases is believed to be responsible for activating STAT5, while in advanced stages development of IL-21 autocrine signaling is thought to be important for STAT3 activation. Recent molecular evidence further suggests that upregulation of STAT5 in early disease stages results in increased expression of oncogenic miR-155 microRNA that subsequently targets STAT4 expression on mRNA level. STAT4 signaling is known to be critical for T helper (Th) 1 phenotype differentiation and its loss results in a switch from Th1 to Th2 phenotype in malignant T cells. During this switch the expression of STAT6 is often upregulated in CTCL. In advanced stages, activation of STAT3 and STAT5 may become completely cytokine-independent and be driven only via constitutively active JAK1 and JAK3 kinases. Further research into the molecular pathogenesis of JAK/STAT signaling in this cancer may enable us to develop effective therapies for our patients.
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http://dx.doi.org/10.4161/15384101.2014.965061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612117PMC
July 2015

Thiurams in shoe contact dermatitis -- a case series.

Contact Dermatitis 2013 Mar;68(3):185-7

Division of Dermatology, McGill University Health Centre, Montréal H3A 1A1, Canada.

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http://dx.doi.org/10.1111/cod.12018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496788PMC
March 2013

Case report: allergic contact cheilitis caused by ceresin wax.

Contact Dermatitis 2012 Jan;66(1):46-7

Department of Dermatology, McGill University Health Centre, Royal Victoria Hospital, Montreal, QC H3A 1A1, Canada.

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http://dx.doi.org/10.1111/j.1600-0536.2011.01983.xDOI Listing
January 2012

Emergent and unusual allergens in cosmetics.

Dermatitis 2010 May-Jun;21(3):127-37

Department of Dermatology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.

Allergic contact dermatitis from cosmetics is a common problem that is occasionally caused by new or rare allergens. When a patient has a positive patch test to a cosmetic product but to none of the common or commercially available allergens, it is important to further patch-test this patient to the ingredients of the product. Thorough testing with the breakdown of ingredients, usually obtained through cooperation with the manufacturer, often allows identification of the culprit allergen in the cosmetic product. In this article, we discuss emerging or rare allergens discovered by this method, including nail lacquer and lipstick allergens, copolymers, shellac, alkyl glucosides, glycols, protein derivatives, idebenone, and octocrylene.
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August 2010