Calum MacAulay

BC Cancer Research Centre, Vancouver, British Columbia, Canada

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Publications (331)958.77 Total impact

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    ABSTRACT: DNA ploidy analysis involves automated quantification of chromosomal aneuploidy, a potential marker of progression toward cervical carcinoma. We evaluated the cost-effectiveness of this method for cervical screening, comparing five ploidy strategies (using different numbers of aneuploid cells as cut points) with liquid-based Papanicolaou smear and no screening. A state-transition Markov model simulated the natural history of HPV infection and possible progression into cervical neoplasia in a cohort of 12-year-old females. The analysis evaluated cost in 2012 US$ and effectiveness in quality-adjusted life-years (QALYs) from a health-system perspective throughout a lifetime horizon in the US setting. We calculated incremental cost-effectiveness ratios (ICERs) to determine the best strategy. The robustness of optimal choices was examined in deterministic and probabilistic sensitivity analyses. In the base-case analysis, the ploidy 4 cell strategy was cost-effective, yielding an increase of 0.032 QALY and an ICER of $18 264/QALY compared to no screening. For most scenarios in the deterministic sensitivity analysis, the ploidy 4 cell strategy was the only cost-effective strategy. Cost-effectiveness acceptability curves showed that this strategy was more likely to be cost-effective than the Papanicolaou smear. Compared to the liquid-based Papanicolaou smear, screening with a DNA ploidy strategy appeared less costly and comparably effective.British Journal of Cancer advance online publication, 28 April 2015; doi:10.1038/bjc.2015.95
    British Journal of Cancer 04/2015; DOI:10.1038/bjc.2015.95 · 4.82 Impact Factor
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    ABSTRACT: Although the Papanicolaou smear has been successful in decreasing cervical cancer incidence in the developed world, there exist many challenges for implementation in the developing world. Quantitative cytology, a semi-automated method that quantifies cellular image features, is a promising screening test candidate. The nested structure of its data (measurements of multiple cells within a patient) provides challenges to the usual classification problem. Here we perform a comparative study of three main approaches for problems with this general data structure: (i) extract patient-level features from the cell-level data, (ii) use a statistical model that accounts for the hierarchical data structure, and (iii) classify at the cellular level and use an ad hoc approach to classify at the patient level. We apply these methods to a dataset of 1728 patients, with an average of 2600 cells collected per patient and 133 features measured per cell, predicting whether a patient had a positive biopsy result. The best approach we found was to classify at the cellular level and count the number of cells that had a posterior probability greater than a threshold value, with estimated 61% sensitivity and 89% specificity on independent data. Recent statistical learning developments allowed us to achieve high accuracy.
    Statistical Analysis and Data Mining 04/2015; DOI:10.1002/sam.11261
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    ABSTRACT: Volatile Organic Compounds (VOC) in exhaled breath as measured by electronic nose (e-nose) have utility as biomarkers to detect subjects at ris of having lung cancer in a screening setting. We hypothesize that breath analysis using an e-nose chemo-resistive sensor array could be used as a screening tool to discriminate patients diagnosed with lung cancer from high-risk smokers. Breath samples from 191 subjects - 25 lung cancer patients and 166 high-risk smoker control subjects without cancer - were analyzed. For clinical relevancy, subjects in both groups were matched for age, sex, and smoking histories. Classification and Regression Trees and Discriminant Functions classifiers were used to recognize VOC patterns in e-nose data. Cross-validated results were used to assess classification accuracy. Repeatability and reproducibility of e-nose data were assessed by measuring subject-exhaled breath in parallel across two e-nose devices. E-nose measurements could distinguish lung cancer patients from high-risk control subjects, with a better than 80% classification accuracy. Subject sex and smoking status impacted classification as area under the curve results (ex-smoker males 0.846, ex-smoker female 0.816, current smoker male 0.745 and current smoker female 0.725) demonstrated. Two e-nose systems could be calibrated to give equivalent readings across subject-exhaled breath measured in parallel. E-nose technology may have significant utility as a non-invasive screening tool for detecting individuals at increased risk for lung cancer. The results presented further the case that VOC patterns could have real clinical utility to screen for lung cancer in the important growing ex-smoker population.
    IEEE transactions on bio-medical engineering 03/2015; DOI:10.1109/TBME.2015.2409092 · 2.23 Impact Factor
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    ABSTRACT: For the first time, we present co-registered autofluorescence imaging and optical coherence tomography (AF/OCT) of excised human palatine tonsils to evaluate the capabilities of OCT to visualize tonsil tissue components. Despite limited penetration depth, OCT can provide detailed structural information about tonsil tissue with much higher resolution than that of computed tomography, magnetic resonance imaging, and Ultrasound. Different tonsil tissue components such as epithelium, dense connective tissue, lymphoid nodules, and crypts can be visualized by OCT. The co-registered AF imaging can provide matching biochemical information. AF/OCT scans may provide a non-invasive tool for detecting tonsillar cancers and for studying the natural history of their development.
    PLoS ONE 12/2014; 9(12):e115889. DOI:10.1371/journal.pone.0115889 · 3.53 Impact Factor
  • Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 11/2014; DOI:10.1016/j.oooo.2014.05.060 · 1.46 Impact Factor
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    ABSTRACT: Purpose: DNA ploidy analysis, a semi-automated process, has been proposed as a potential alternative for cervical screening; however, this strategy has not been evaluated economically. Our study examined the cost-effectiveness of ploidy analysis in comparison to liquid-based Papanicolaou (Pap) smear in the screening setting. Methods: The use of ploidy was examined with five thresholds corresponding to the number (from 1 to 5) of aneuploid cells in a specimen. For example, the ploidy 3 cell strategy rendered a specimen abnormal if at least 3 aneuploid cells were found. We compared these five ploidy strategies and the liquid-based Pap smear with a no screening strategy as the reference. We developed a state-transition Markov model to simulate the natural history of HPV infection and possible progression into cervical neoplasia in a hypothetical cohort of 12-year-old females (started triennial screening from 21 years). The analysis was conducted using cost in 2012 US$ and effectiveness in quality-adjusted life-years (QALYs) from a health-system perspective throughout a lifetime horizon in the US setting. The willingness-to-pay threshold was $50,000/QALY. We calculated the incremental cost-effectiveness ratios (ICERs) for the various strategies to determine the best ploidy strategy and the overall recommended strategy. The robustness of optimal choices was examined in deterministic and probabilistic sensitivity analyses. Results: In the base-case analysis, the ploidy 4 cell strategy was cost-effective. It increased the quality-adjusted life expectancy by 0.083 QALY and yielded an ICER of $8,774/QALY compared to the no screening strategy. In the deterministic sensitivity analysis, the cost-effectiveness was most sensitive to the cost of the Pap smear procedure, the cost of treating high-grade squamous intraepithelial lesions, the cost of the ploidy analysis, and the ploidy strategies' operating characteristics. For most scenarios, the ploidy 4 cell strategy was cost-effective and was considered the best ploidy strategy. The cost-effectiveness acceptability curves showed that the ploidy 4 cell strategy was more likely to be cost-effective than the Pap smear strategy. Conclusion: Compared to liquid-based Pap smear screening, ploidy analysis appeared less costly and comparably effective using the standard willingness-to-pay threshold. Screening for cervical neoplasia using DNA ploidy analysis may be a satisfactory alternative, particularly in low-infrastructure settings. Figure 1. Cost-effectiveness acceptability curves comparing no screening, Papanicolaou smear screening, and the ploidy 4 cell strategy.
    The 36th Annual Meeting of the Society for Medical Decision Making; 10/2014
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    ABSTRACT: Worldwide, oral cancer is responsible for 170,000 deaths per year. Intervention to prevent this disease is a long sought after goal. Chemoprevention studies have focused on clinicopathological features of potentially malignant lesions (PML) in an effort to prevent their progression to cancer. However, prediction of future behavior for such lesions is difficult and remains a major challenge to such intervention. Different approaches to this problem have been tested in the past 20years. Early genetic progression models identified critical regions of allelic imbalance at 3p and 9p, and provided the basis for molecular markers to identify progressing PMLs. Subsequently, technological advances, such as genome-wide high-throughput array platforms, computer imaging, visualization technology and next generation sequencing, have broadened the scope for marker development and have the potential of further improving our ability to identify high-risk lesions in the near future either alone or in combination. In this article, we examine the milestones in the development of markers for PML progression. We emphasize the critical importance of networks among scientists, health professionals and community to facilitate the validation and application of putative markers into clinical practice. With a growing number of new agents to validate, it is necessary to coordinate the design and implementation of strategies for patient recruitment, integration of marker assessment, and the final translation of such approaches into clinical use.
    Oral Oncology 09/2014; DOI:10.1016/j.oraloncology.2014.08.012 · 3.03 Impact Factor
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    ABSTRACT: Accurate cervical intra-epithelial neoplasia (CIN) lesion grading is needed for effective patient management. We applied computer-assisted scanning and analytic approaches to immuno-stained CIN lesion sections to more accurately delineate disease states and decipher cell proliferation impacts from HPV and smoking within individual epithelial layers. A patient cohort undergoing cervical screening was identified (n = 196) and biopsies of varying disease grades and with intact basement membranes and epithelial layers were obtained (n = 261). Specimens were sectioned, stained (Mib1), and scanned using a high-resolution imaging system. We achieved semi-automated delineation of proliferation status and epithelial cell layers using Otsu segmentation, manual image review, Voronoi tessellation, and immuno-staining. Data were interrogated against known status for HPV infection, smoking, and disease grade. We observed increased cell proliferation and decreased epithelial thickness with increased disease grade (when analyzing the epithelium at full thickness). Analysis within individual cell layers showed a ≥50% increase in cell proliferation for CIN2 vs. CIN1 lesions in higher epithelial layers (with minimal differences seen in basal/parabasal layers). Higher rates of proliferation for HPV-positive vs. -negative cases were seen in epithelial layers beyond the basal/parabasal layers in normal and CIN1 tissues. Comparing smokers vs. non-smokers, we observed increased cell proliferation in parabasal (low and high grade lesions) and basal layers (high grade only). In sum, we report CIN grade-specific differences in cell proliferation within individual epithelial layers. We also show HPV and smoking impacts on cell layer-specific proliferation. Our findings yield insight into CIN progression biology and demonstrate that rigorous, semi-automated imaging of histopathological specimens may be applied to improve disease grading accuracy.
    PLoS ONE 09/2014; 9(9):e107088. DOI:10.1371/journal.pone.0107088 · 3.53 Impact Factor
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    ABSTRACT: We present a power-efficient fiber-based imaging system capable of co-registered autofluorescence imaging and optical coherence tomography (AF/OCT). The system employs a custom fiber optic rotary joint (FORJ) with an embedded dichroic mirror to efficiently combine the OCT and AF pathways. This three-port wavelength multiplexing FORJ setup has a throughput of more than 83% for collected AF emission, significantly more efficient compared to previously reported fiber-based methods. A custom 900 µm diameter catheter ‒ consisting of a rotating lens assembly, double-clad fiber (DCF), and torque cable in a stationary plastic tube ‒ was fabricated to allow AF/OCT imaging of small airways in vivo. We demonstrate the performance of this system ex vivo in resected porcine airway specimens and in vivo in human on fingers, in the oral cavity, and in peripheral airways.
    Biomedical Optics Express 09/2014; 5(9). DOI:10.1364/BOE.5.002978 · 3.50 Impact Factor
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    ABSTRACT: BackgroundMicroRNAs (miRNAs) are non-coding RNAs that negatively regulate gene expression by preventing the translation of specific mRNA transcripts. Recent studies have shown that miRNAs are stably expressed in human serum samples, making them good candidates for the non-invasive detection of disease. However, before circulating miRNAs can be used reliably as biomarkers of disease, the pre-measurement variables that may affect serum miRNA levels must be assessed.MethodsIn this study we used quantitative RT-PCR to examine the effect of hemolysis, fasting, and smoking on the levels of 742 miRNAs in the serum of healthy individuals. We also compared serum miRNA profiles of samples taken from healthy individuals over different time periods to assess normal serum miRNA fluctuations.ResultsWe have found that mechanical hemolysis of blood samples can significantly alter serum miRNA quantification and have identified 162 miRNAs that are significantly up-regulated in hemolysed serum samples. Conversely, fasting and smoking were demonstrated to not have a significant effect on the overall serum miRNA profiles of healthy individuals. The serum miRNA profiles of matched samples taken from individuals over varying time periods showed a high correlation and no miRNAs were significantly differentially expressed in these samples further suggesting the utility of serum miRNAs as biomarkers of disease. Taking the above results into consideration, we have identified miR-99a-5p and miR-139-5p as novel endogenous controls for serum miRNA studies due to their consistency across all sample sets.ConclusionThese results identify important pre-profiling factors that should be taken into consideration when identifying endogenous controls and candidate biomarkers for circulating miRNA studies.
    BMC Clinical Pathology 06/2014; 14:27. DOI:10.1186/1472-6890-14-27
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    ABSTRACT: Examining and quantifying changes in airway morphology is critical for studying longitudinal pathogenesis and interventions in diseases such as chronic obstructive pulmonary disease and asthma. Here we present fiber-optic optical coherence tomography (OCT) as a nondestructive technique to precisely and accurately measure the 2-dimensional cross-sectional areas of airway wall substructure divided into the mucosa (WAmuc), submucosa (WAsub), cartilage (WAcart), and the airway total wall area (WAt). Porcine lung airway specimens were dissected from freshly resected lung lobes (N = 10). Three-dimensional OCT imaging using a fiber-optic rotary-pullback probe was performed immediately on airways greater than 0.9 mm in diameter on the fresh airway specimens and subsequently on the same specimens post-formalin-fixation. The fixed specimens were serially sectioned and stained with H&E. OCT images carefully matched to selected sections stained with Movat's pentachrome demonstrated that OCT effectively identifies airway epithelium, lamina propria, and cartilage. Selected H&E sections were digitally scanned and airway total wall areas were measured. Traced measurements of WAmuc, WAsub, WAcart, and WAt from OCT images of fresh specimens by two independent observers found there were no significant differences (p>0.05) between the observer's measurements. The same wall area measurements from OCT images of formalin-fixed specimens found no significant differences for WAsub, WAcart and WAt, and a small but significant difference for WAmuc. Bland-Altman analysis indicated there were negligible biases between the observers for OCT wall area measurements in both fresh and formalin-fixed specimens. Bland-Altman analysis also indicated there was negligible bias between histology and OCT wall area measurements for both fresh and formalin-fixed specimens. We believe this study sets the groundwork for quantitatively monitoring pathogenesis and interventions in the airways using OCT.
    PLoS ONE 06/2014; 9(6):e100145. DOI:10.1371/journal.pone.0100145 · 3.53 Impact Factor
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    ABSTRACT: We report a polarization diversity detection scheme for optical coherence tomography with a new, custom, miniaturized fiber coupler with single mode (SM) fiber inputs and polarization maintaining (PM) fiber outputs. The SM fiber inputs obviate matching the optical lengths of the X and Y OCT polarization channels prior to interference and the PM fiber outputs ensure defined X and Y axes after interference. Advantages for this scheme include easier alignment, lower cost, and easier miniaturization compared to designs with free-space bulk optical components. We demonstrate the utility of the detection system to mitigate the effects of rapidly changing polarization states when imaging with rotating fiber optic probes in Intralipid suspension and during in vivo imaging of human airways.
    Optics Letters 06/2014; 39(12):3638-3641. DOI:10.1364/OL.39.003638 · 3.18 Impact Factor
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    ABSTRACT: A major challenge for the early diagnosis of oral cancer is the ability to differentiate oral premalignant lesions (OPL) at high risk of progressing into invasive squamous cell carcinoma (SCC) from those at low risk. Our group has previously used high-resolution image analysis algorithms to quantify the nuclear phenotypic changes occurring in OPLs. This approach, however, requires a manual selection of nuclei images. Here, we investigated a new, semi-automated algorithm to identify OPLs at high risk of progressing into invasive SCC from those at low risk using Random Forests, a tree-based ensemble classifier. We trained a sequence of classifiers using morphometric data calculated on nuclei from 29 normal, 5 carcinoma in situ (CIS) and 28 SCC specimens. After automated discrimination of nuclei from other objects (i.e., debris, clusters, etc.), a nuclei classifier was trained to discriminate abnormal nuclei (8,841) from normal nuclei (5,762). We extracted voting scores from this trained classifier and created an automated nuclear phenotypic score (aNPS) to identify OPLs at high risk of progression. The new algorithm showed a correct classification rate of 80 % (80.6 % sensitivity, 79.3 % specificity) at the cellular level for the test set, and a correct classification rate of 75 % (77.8 % sensitivity, 71.4 % specificity) at the tissue level with a negative predictive value of 76 % and a positive predictive value of 74 % for predicting progression among 71 OPLs, performed on par with the manual method in our previous study. We conclude that the newly developed aNPS algorithm serves as a crucial asset in the implementation of high-resolution image analysis in routine clinical pathology practice to identify lesions that require molecular evaluation or more frequent follow-up.
    05/2014; 37(3). DOI:10.1007/s13402-014-0172-x
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    ABSTRACT: We are investigating spectroscopic devices designed to make in vivo cervical tissue measurements to detect pre-cancerous and cancerous lesions. All devices have the same design and ideally should record identical measurements. However, we observed consistent differences among them. An experiment was designed to study the sources of variation in the measurements recorded. Here we present a log additive statistical model that incorporates the sources of variability we identified. Based on this model, we estimated correction factors from the experimental data needed to eliminate the inter-device variability and other sources of variation. These correction factors are intended to improve the accuracy and repeatability of such devices when making future measurements on patient tissue.
    Optics Express 04/2014; 22(7):7617-24. DOI:10.1364/OE.22.007617 · 3.53 Impact Factor
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    ABSTRACT: Autofluorescence (AF) imaging can provide valuable information about the structural and metabolic state of tissue that can be useful for elucidating physiological and pathological processes. Optical coherence tomography (OCT) provides high resolution detailed information about tissue morphology. We present coregistered AF-OCT imaging of human lung sections. Adjacent hematoxylin and eosin stained histological sections are used to identify tissue structures observed in the OCT images. Segmentation of these structures in the OCT images allowed determination of relative AF intensities of human lung components. Since the AF imaging was performed on tissue sections perpendicular to the airway axis, the results show the AF signal originating from the airway wall components free from the effects of scattering and absorption by overlying layers as is the case during endoscopic imaging. Cartilage and dense connective tissue (DCT) are found to be the dominant fluorescing components with the average cartilage AF intensity about four times greater than that of DCT. The epithelium, lamina propria, and loose connective tissue near basement membrane generate an order of magnitude smaller AF signal than the cartilage fluorescence.
    Journal of Biomedical Optics 03/2014; 19(3):36022. DOI:10.1117/1.JBO.19.3.036022 · 2.75 Impact Factor
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    ABSTRACT: Dysplastic progression in epithelial tissues is linked to changes in morphology and internal structure of cell nuclei. These changes lead to alterations in nuclear light scattering profiles that can potentially be monitored for diagnostic purposes. Numerical tools allow for simulation of complex nuclear models and are particularly useful for quantifying the optical response of cell nuclei as dysplasia progresses. In this study, we first analyze a set of quantitative histopathology images from twenty cervical biopsy sections stained with Feulgen-thionin. Since Feulgen-thionin is stoichiometric for DNA, the images enable us to obtain detailed information on size, shape, and chromatin content of all the segmented nuclei. We use this extensive data set to construct realistic three-dimensional computational models of cervical cell nuclei that are representative of four diagnostic categories, namely normal or negative for dysplasia, mild dysplasia, moderate dysplasia, and severe dysplasia or carcinoma in situ (CIS). We then carry out finite-difference time-domain simulations to compute the light scattering response of the constructed models as a function of the polar scattering angle and the azimuthal scattering angle. The results show that these two-dimensional scattering patterns exhibit characteristic intensity ridges that change form with progression of dysplasia; pattern processing reveals that Haralick features can be used to distinguish moderately and severely dysplastic or CIS nuclei from normal and mildly dysplastic nuclei. Our numerical study also suggests that different angular ranges need to be considered separately to fully exploit the diagnostic potential of two-dimensional light scattering measurements.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2014; DOI:10.1117/12.2041281 · 0.20 Impact Factor
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    ABSTRACT: The objective was to develop an automated optical coherence tomography (OCT) segmentation method. We evaluated three ex-vivo porcine airway specimens; six non-sequential OCT images were selected from each airway specimen. Histology was also performed for each airway and histology images were co-registered to OCT images for comparison. Manual segmentation of the airway luminal area, mucosa area, submucosa area and the outer airway wall area were performed for histology and OCT images. Automated segmentation of OCT images employed a despecking filter for pre-processing, a hessian-based filter for lumen and outer airway wall area segmentation, and K-means clustering for mucosa and submucosa area segmentation. Bland-Altman analysis indicated that there was very little bias between automated OCT segmentation and histology measurements for the airway lumen area (bias=-6%, 95% CI=-21%-8%), mucosa area, (bias=-4%, 95% CI=-14%-5%), submucosa area (bias=7%, 95% CI=-7%-20%) and outer airway wall area segmentation results (bias=-5%, 95% CI=-14%-5%). We also compared automated and manual OCT segmentation and Bland-Altman analysis indicated that there was negligible bias between luminal area (bias=4%, 95% CI=1%-8%), mucosa area (bias=-3%, 95% CI=-6%-1%), submucosa area (bias=-2%, 95% CI=-10%-6%) and the outer airway wall (bias=-3%, 95% CI=-13%-6%). The automated segmentation method for OCT airway imaging developed here allows for accurate and precise segmentation of the airway wall components, suggesting that translation of this method to in vivo human airway analysis would allow for longitudinal and serial studies.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2014; DOI:10.1117/12.2040866 · 0.20 Impact Factor
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    ABSTRACT: New imaging technologies are changing the field of digital pathology. This field faces numerous challenges and there is a pressing need for standardization, calibration protocols, quality control and quantitative assessment. We have designed a new calibration imaging slide (Cancer Imaging Slide), specifically to measure the characteristics of old or new imaging systems or scanners. The layout of the slide consists of 138 boxes with the side length of 1.6 mm, containing objects of known morphologic and photometric characteristics. Among them, 112 boxes contain different permutations of circles, ovals, and squares. The circles have different radii, radius/pitch ratios and step transmissions. The ovals have different sizes and orientations. The squares are consistent in size and orientation but have different step transmission values. Also, 16 boxes contain three resolution test targets: crosses, USAF target and Siemens star. The last 10 boxes are blank boxes with different transmission values. Four slides were scanned and imaged on one commercial whole-slide scanner and one high resolution imaging system. After segmenting the images, about 200 features (photometric, morphologic and architectural) were measured with our in-house image processing software. The objective of the project is to develop a statistical process control using this new slide. In this paper, we describe the characteristics of the slide and present our preliminary results.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2014; DOI:10.1117/12.2041310 · 0.20 Impact Factor
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    ABSTRACT: We use an extensive set of quantitative histopathology data to construct realistic three-dimensional models of normal and dysplastic cervical cell nuclei at different epithelial depths. We then employ the finite-difference time-domain method to numerically simulate the light scattering response of these representative models as a function of the polar and azimuthal scattering angles. The results indicate that intensity and shape metrics computed from two-dimensional scattering patterns can be used to distinguish between different diagnostic categories. Our numerical study also suggests that different epithelial layers and angular ranges need to be considered separately to fully exploit the diagnostic potential of two-dimensional light scattering measurements.
    Biomedical Optics Express 02/2014; 5(2):485-98. DOI:10.1364/BOE.5.000485 · 3.50 Impact Factor
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    ABSTRACT: Formalin-fixed tissue has been a mainstay of clinical pathology laboratories, but formalin alters many biomolecules, including nucleic acids and proteins. Meanwhile, frozen tissues contain better-preserved biomolecules, but tissue morphology is affected, limiting their diagnostic utility. Molecular fixatives promise to bridge this gap by simultaneously preserving morphology and biomolecules, enabling clinical diagnosis and molecular analyses on the same specimen. While previous reports have broadly evaluated the use of molecular fixative in various human tissues, we present here the first detailed assessment of the applicability of molecular fixative to both routine histopathological diagnosis and molecular analysis of cervical tissues. Ten specimens excised via the Loop Electrosurgical Excision Procedure, which removes conical tissue samples from the cervix, were cut into alternating pieces preserved in either formalin or molecular fixative. Cervical specimens preserved in molecular fixative were easily interpretable, despite featuring more eosinophilic cytoplasm and more recognizable chromatin texture than formalin-fixed specimens. Immunohistochemical staining patterns of p16 and Ki-67 were similar between fixatives, although Ki-67 staining was stronger in the molecular fixative specimens. The RNA of molecular fixative specimens from seven cases representing various dysplasia grades was assessed for utility in expression microarray analysis. Cluster analysis and scatter plots of duplicate samples suggest that data of sufficient quality can be obtained from as little as 50ng of RNA from molecular fixative samples. Taken together, our results show that molecular fixative may be a more versatile substitute for formalin, simultaneously preserving tissue morphology for clinical diagnosis and biomolecules for immunohistochemistry and gene expression analysis.
    Experimental and Molecular Pathology 01/2014; 96(2). DOI:10.1016/j.yexmp.2013.12.007 · 2.88 Impact Factor

Publication Stats

6k Citations
958.77 Total Impact Points


  • 1988–2014
    • BC Cancer Research Centre
      • Integrative Oncology Department
      Vancouver, British Columbia, Canada
    • University of British Columbia - Vancouver
      • • Cell and Developmental Biology (CELL)
      • • Department of Obstetrics and Gynaecology
      • • Department of Pathology and Laboratory Medicine
      • • Division of Respiratory Medicine
      • • Department of Dermatology and Skin Science
      • • Faculty of Medicine
      Vancouver, British Columbia, Canada
  • 2013
    • Second University of Naples
      Caserta, Campania, Italy
  • 1991–2013
    • BC Cancer Agency
      Vancouver, British Columbia, Canada
  • 2007
    • University of Santiago, Chile
      CiudadSantiago, Santiago Metropolitan, Chile
    • Vancouver Coastal Health
      Vancouver, British Columbia, Canada
    • University of Houston
      Houston, Texas, United States
  • 2002–2007
    • Rice University
      Houston, Texas, United States
  • 2006
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
  • 2004–2006
    • University of Texas at Dallas
      Richardson, Texas, United States
    • Michael Smith Genome Sciences Centre
      Calgary, Alberta, Canada
  • 2002–2006
    • University of Texas at Austin
      • • Department of Biomedical Engineering
      • • Department of Electrical & Computer Engineering
      Austin, Texas, United States
  • 2005
    • The International Society for Optics and Photonics
      International Falls, Minnesota, United States
  • 2003–2005
    • University of Texas MD Anderson Cancer Center
      • Biomedical Engineering
      Houston, TX, United States
  • 1994
    • University of Guelph
      • College of Biological Science
      Guelph, Ontario, Canada
  • 1992
    • The University of Manchester
      Manchester, England, United Kingdom