Gina Lockwood

Interactive digital slides with heat maps: a novel method to improve the reproducibility of Gleason grading

Our aims were to analyze reporting of Gleason pattern (GP) 3 and 4 prostate cancer with the ISUP 2005 Gleason grading and to collect consensus cases for standardization. We scanned 25 prostate biopsy cores diagnosed as Gleason score (GS) 6–7. Fifteen genitourinary pathologists graded the digital slides and circled GP 4 and 5 in a slide viewer. Grading difficulty was scored as 1–3. GP 4 components were classified as type 1 (cribriform), 2 (fused), or 3 (poorly formed glands). A GS of 5–6, 7 (3 + 4), 7 (4 + 3), and 8–9 was given in 29%, 41%, 19%, and 10% (mean GS 6.84, range 6.44–7.36). In 15 cases, at least 67% of observers agreed on GS groups (consensus cases). Mean interobserver weighted kappa for GS groups was 0.43. Mean difficulty scores in consensus and non-consensus cases were 1.44 and 1.66 (p = 0.003). Pattern 4 types 1, 2, and 3 were seen in 28%, 86%, and 67% of GP 4. All three coexisted in 16% (11% and 23% in consensus and non-consensus cases, p = 0.03). Average estimated and calculated %GP 4/5 were 29% and 16%. After individual review, the experts met to analyze diagnostic difficulties. Areas of GP 4 and 5 were displayed as heat maps, which were helpful for identifying contentious areas. A key problem was to agree on minimal criteria for small foci of GP 4. In summary, the detection threshold for GP 4 in NBX needs to be better defined. This set of consensus cases may be useful for standardization.

Operator is an Independent Predictor of Detecting Prostate Cancer at Transrectal Ultrasound Guided Prostate Biopsy

PURPOSE We investigated whether interoperator differences exist in the setting of prostate cancer detection by transrectal ultrasound guided prostate biopsy. Our secondary aim was to investigate whether a learning curve exists for prostate cancer detection. MATERIALS AND METHODS A prospective database from 2000 to 2008 including 9,072 transrectal ultrasound guided prostate biopsies at our institution was limited to 4,724 done at initial presentation. Biopsies were performed by 4 uroradiologists. The OR for detecting cancer on transrectal ultrasound guided prostate biopsy was calculated for likely independent prognostic variables, including operator. We also examined the rate of biopsy positivity in increments, comparing the first and last cohorts. The senior radiologist (AT) with the most biopsies (75%) was considered the referent for prostate cancer detection. Univariate and multivariate logistic regression modeling was used to determine significant covariates with p <0.05 deemed relevant. RESULTS Prostate cancer was detected in 2,331 men (49.3%). Operators performed a median of 514 transrectal ultrasound guided prostate biopsies (range 187 to 3,509) with a prostate cancer detection rate of 43.8% to 52.4% (p = 0.001). Other significant covariates were prostate specific antigen, suspicious lesions on ultrasound, nodule on digital rectal examination, smaller prostate volume and increasing patient age. Operator was a significant multivariate predictor of cancer detection (OR 0.67 to 0.89, p = 0.003). No learning curve was detected and biopsy rates were consistent throughout the series. CONCLUSIONS Significant differences in prostate cancer detection exist among operators who perform transrectal ultrasound guided prostate biopsy even in the same setting. The volume of previously performed transrectal ultrasound guided prostate biopsies does not appear to influence the positive prostate cancer detection rate, nor could a learning curve be identified. Differences in prostate cancer detection among operators are likely related to unknown differences in expertise or technique. Further research is needed.

Measurement of peri‐prostatic fat thickness using transrectal ultrasonography (TRUS): a new risk factor for prostate cancer

Study Type – Prognosis (cohort)

Immunohistochemical examination of the mTORC1 pathway in high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinomas (PCa): A tissue microarray study (TMA)

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and a key regulator of protein synthesis and growth and is upregulated in many cancers. mTOR is activated by AKT phosphorylation (p‐mTOR). p‐mTOR associates with regulatory‐associated protein of TOR (RAPTOR), forming the mTORC1 complex. mTORC1 promotes the activation of p70 ribosomal protein s6 kinase 1 (p70S6K1) and ribosomal protein s6 (RPS6). Upregulation of this pathway can lead to an aberrant increase in cell growth and metabolism characteristic of malignant transformation.

mTOR–RAPTOR and 14-3-3σ immunohistochemical expression in high grade prostatic intraepithelial neoplasia and prostatic adenocarcinomas: a tissue microarray study

Background The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase which associates with regulatory-associated protein of TOR (RAPTOR), forming the mTORC1 complex, which is necessary for activation of the mTOR pathway. 14-3-3σ belongs to a family of proteins known to regulate the mTOR–RAPTOR interaction and signalling of this cascade. The mTOR pathway is a key regulator of protein synthesis and growth and is up-regulated in many cancers. The correlation of mTOR, RAPTOR and 14-3-3σ in high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer has not previously been investigated. Aims To examine the immunohistochemical expression of phosphorylated mTOR (p-mTOR), RAPTOR and 14-3-3σ in HGPIN and prostatic adenocarcinoma (PCa) using tissue microarrays. Methods and results There were contrasting immunohistochemical patterns of expression for mTOR and 14-3-3σ in HGPIN and PCa. Cochran–Armitage analysis demonstrated decreasing p-mTOR and increasing 14-3-3σ expression, progressing from PIN through GL6 and GL7 to high grade PCa. In cores with coexistent staining for 14-3-3σ and p-mTOR, the expression of each marker was restricted to different geographical areas of an individual core. Conclusion The inverse correlation of p-mTOR and 14-3-3σ expression supports the role of 14-3-3σ as an inhibitor of p-mTOR activity in the prostate. The extent of 14-3-3σ and mTOR expression in an individual patient with prostate cancer would determine how effective the use of mTOR inhibitors would be as potential therapeutic agents.

Rates of cancer incidence across terciles of the foreign-born population in Canada from 2001-2006.

ObjectivesTo address the issue of comparative risk of cancer in Canada’s immigrant population, an area-based methodology was applied to examine whether or not estimated cancer incidence rates among individuals living in given areas vary systematically according to the concentration of foreignborn individuals living in the same area. This method provides an alternative, accessible surveillance method in the absence of linked individual-level information to extend the work of others by providing both national and subnational standardized, hence comparable, results to address this issue.MethodsCanadian Cancer Registry data (2001 to 2006) and 2006 Census data provided dissemination area information regarding the concentration of the foreign-born population and population estimates for rate denominators. Cancer (all cause and cause-specific) incidence rate ratios (agestandardized and by age/sex) were calculated by foreign-born concentration areas at both national and regional levels.ResultsAn inverse gradient was identified between cancer incidence rates and area concentration of foreign-born, with the all-sites cancer rate ranging from a low of 388 per 100,000 among individuals living in areas with a high concentration of foreign-born to a high of 493 per 100,000 among individuals living in areas with a low concentration of foreign-born. This pattern occurred nationally for lung, colorectal, prostate and female breast cancers. However, for liver, nasopharynx, and thyroid cancers, higher cancer rates were observed in areas with a higher versus lower concentration of foreign-born populations.ConclusionThe study findings provide suggestive evidence of decreased cancer risk among foreign-born populations for most cancers except nasopharynx, liver and thyroid for which risks were higher. The results of this study demonstrate the value of ecological-based methods for disease surveillance in the absence of individual-level information on immigrant status in the national cancer registry.RésuméObjectifsPour aborder la question du risque comparatif de cancer dans la population immigrante du Canada, nous avons appliqué une méthode régionale pour déterminer si les taux d’incidence estimatifs du cancer chez les résidents de certaines régions varient systématiquement selon la concentration de personnes nées à l’étranger vivant dans la même région. En l’absence de données individuelles maillées, une telle méthode offre une solution de surveillance accessible pour compléter le travail d’autres chercheurs; elle offre des résultats à la fois nationaux et sousnationaux standardisés, et donc comparables, pour aborder la question.MéthodeLes données du Registre canadien du cancer (2001 à 2006) et celles du Recensement de 2006 ont fourni de l’information par aire de diffusion sur la concentration de personnes nées à l’étranger et des estimations démographiques pour les dénominateurs des taux. Les ratios des taux d’incidence (standardisés pour l’âge et pour l’âge/le sexe) du cancer (toutes causes confondues et par cause) ont été calculés pour chaque zone de concentration de personnes nées à l’étranger à l’échelle nationale et régionale.RésultatsNous avons observé un gradient inversé entre les taux d’incidence du cancer et la concentration régionale de personnes nées à l’étranger: les taux de cancer tous sites confondus variaient de 388 p. 100 000 (chez les résidents des régions à forte concentration de personnes nées à l’étranger) à 493 p. 100 000 (chez les résidents des régions à faible concentration de personnes nées à l’étranger). Cette tendance se manifestait à l’échelle nationale pour les cancers du poumon, colorectal et de la prostate et pour le cancer du sein féminin. Toutefois, pour les cancers du foie, du nasopharynx et de la thyroïde, nous avons observé des taux de cancer supérieurs dans les régions à forte plutôt qu’à faible concentration de personnes nées à l’étranger.ConclusionLes constatations de l’étude donnent à penser que le risque de cancer est réduit au sein des populations nées à l’étranger pour la plupart des cancers sauf ceux du nasopharynx, du foie et de la thyroïde, pour lesquels les risques sont supérieurs. Ces résultats démontrent la valeur des méthodes écologiques pour la surveillance des maladies en l’absence de données individuelles sur le statut d’immigrant dans le registre national du cancer.

Conditional relative survival: a different perspective to measuring cancer outcomes.

Lorraine Shack *, Heather Bryant , Gina Lockwood , Larry F. Ellison d a Population and Public Health, Alberta Health Services, Calgary, Canada Divisions of Oncology and Community Health Sciences, University of Calgary, Calgary, Canada Canadian Partnership Against Cancer, 1 University Ave., Suite 300, Toronto, ON M5J 2P1, Canada Health Statistics Division, Statistics Canada, Ottawa, ON, Canada