Sandy Liu

Correlation of p16 expression and HPV type with survival in oropharyngeal squamous cell cancer

OBJECTIVES Examine the effect of concordance between p16 overexpression and HR (high risk) HPV DNA status on overall survival in a large series of oropharyngeal squamous cell carcinoma (OPSCC) cases. MATERIALS AND METHODS A total of 185 patients with primary OPSCC had genomic DNA tested by PCR for the HPV16 E6 and E7 oncogenes. 184 of 185 patients had p16 IHC performed. Linear array HPV genotyping was performed in all 21 HPV16/p16 discordant cases (HPV16+/p16- or HPV16-/p16+) as well as in 43 control cases. RESULTS 73 of 185 patients were positive for HR HPV (39%). Six of 73 HPV infections were due to HR HPV types other than HPV16: types 31 (1), 33 (2), 51 (1), 58 (1), and 59 (1); all 6 cases were p16 positive. p16 IHC was concordant with HR HPV testing in 169 of 184 cases (92%), and had a sensitivity and specificity of 92% and 92%. HR HPV+/p16+ and discordant HR HPV/p16 patients had significantly improved overall survival compared to HR HPV-/p16- patients. CONCLUSION p16 IHC is a reliable surrogate marker for HR HPV testing in OPSCC. Prognostically favorable HR HPV genotypes other than HPV16 are reflected in p16 positivity.

Diffuse mesothelioma of the peritoneum: correlation between histological and clinical parameters and survival in 73 patients

Summary There are few studies addressing survival of diffuse peritoneal mesotheliomas (DPM). In this study, survival data were obtained retrospectively from 73 patients treated with intended cytoreductive surgery for DPM, with a mean follow-up of 42 months. Mesotheliomas were classified as well differentiated papillary (WDPM, n = 2), multicystic (MCM, n = 4), and epithelioid mesotheliomas were subclassified as tubulopapillary (TPM, n = 27), solid/deciduoid (S/DM, n = 34), and or biphasic mesothelioma (BPM, n = 6). Invasion was characterised as absent (grade 0), into stroma (grade 1), into fat (grade 2), and into adjacent structures (grade 3). Peritoneal cancer index (PCI) and completeness of cytoreduction (CCR) were assessed surgically. There were no deaths in the WDPM, MCM, and epithelioid DPM with ⩽ grade 1 invasion. There was a stepwise decrease in overall survival from invasive TPM, S/DM, and BPM (p < 0.0001). By univariate analysis, advanced age (p = 0.01), incomplete CCR (p < 0.001), PCI (p = 0.004), mitotic count (p < 0.001), nuclear grade (p < 0.0001), stromal inflammation (p = 0.013), depth of invasion (p < 0.0001), necrosis (p = 0.002), and sarcomatoid growth (p < 0.0001) were associated with decreased overall survival. By multivariate analysis, only sarcomatoid growth (p = 0.0006), depth of invasion (p = 0.02), elevated CCR (CCR 2–3) (p = 0.02), and presence of inflammatory stroma (p = 0.04) were significant variables associated with decreased overall survival. DPM form a spectrum of indolent to highly aggressive tumours. Solid epithelioid/deciduoid tumours have a prognosis intermediate between biphasic mesotheliomas and invasive TPM. The presence and degree of invasion, sarcomatoid features, and inflammatory stroma are poor prognostic indicators.

Emergence of HPV16-positive oropharyngeal cancer in Black patients over time: University of Maryland 1992-2007.

While we previously reported a striking racial difference in the prevalence of human papilloma virus (HPV)–positive squamous cell carcinoma of the oropharynx (OPSCC), less is known about differences in outcomes and trends over time in OPSCC by HPV status and race. We conducted a retrospective analysis of 467 patients with OPSCC treated at the University of Maryland Greenebaum Cancer Center (Baltimore, MD) between 1992 and 2007, of which 200 had tissue available for HPV16 testing. HPV16-positive patients were significantly more likely to be white, with 45.5% of whites and 15.5% of blacks testing positive for HPV16. There was a significant increase in HPV16-positive OPSCC for all patients over time from 15.6% in 1992 to 1995 to 43.3% in 2004 to 2007 (P = 0.01). From 1992 to 1995, 33% of white patients were HPV16-positive, with no black patients positive. From 2004 to 2007, 17.7% of black patients and 54% of white patients were HPV16-positive. White and black patients with HPV16-positive tumors had an identical and favorable overall survival (OS; median, 8.1 and 8.1 years, respectively). However, among HPV16-negative patients, whites had an improved OS compared with blacks (median, 2.3 vs. 0.9 years, respectively; P = 0.02), including when analyzed in a multivariable Cox regression model. From 1992 to 2007, the percentage of HPV16-positive OPSCC increased for white patients and was seen for the first time in black patients. While survival for HPV-positive black and white patients was similar and favorable, outcomes for HPV-negative patients were poor, with blacks having worse survival even after controlling for baseline characteristics.Cancer Prev Res; 8(1); 12–19. ©2014 AACR. See related article by E. Cohen and C. Fakhry, p. 9

Role of image-guided patient repositioning and online planning in localized prostate cancer IMRT

PURPOSE To determine the expected benefit of image-guided online replanning over image-guided repositioning of localized prostate cancer intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS On 10 to 11 CT scans of each of 10 early-stage prostate cancer patients, the prostate, bladder and rectum are manually segmented. Using a 3-mm PTV margin expansion from the CTV, an IMRT plan is made on the first CT scan of each patient. Online repositioning is simulated by recalculating the IMRT plan from the initial CT scan on the subsequent CT scans of each patient. For online replanning, IMRT is replanned twice on all CT scans, using 0-mm and 3-mm margins. The doses from subsequent CT images of each patient are then deformed to the initial CT anatomy using a mesh-based thin-plate B-spline deformation method and are accumulated for DVH and isodose review. RESULTS Paired t-tests show that online replanning with 3-mm margins significantly increases the prostate volume receiving the prescribed dose over replanning with 0-mm margins (p-value 0.004); gives marginally better target coverage than repositioning with 3-mm margins(p-value 0.06-0.343), and reduces variations in target coverage over repositioning. Fractional volumes of rectum and bladder receiving 75%, 80%, 85%, 90%, and 95% (V75, V80, V85, V90, and V95) of the prescription dose are evaluated. V90 and V95 values for the rectum are 1.6% and 0.7 % for 3-mm margin replanning and 1% and 0.4 % for 0-mm margin replanning, with p-values of 0.010-0.011. No significant differences between repositioning and replanning with 3-mm margins are found for both the rectum and the bladder. CONCLUSIONS Image-guided replanning using 3-mm margins reduces target coverage variations, and maintains comparable rectum and bladder sparing to patient repositioning in localized prostate cancer IMRT. Marginal reductions in doses to rectum and bladder are possible when planning margins are eliminated in the online replanning scenario. However, further reduction in treatment planning margins is not recommended.

Polyomavirus Replication and Smoking Are Independent Risk Factors for Bladder Cancer After Renal Transplantation.

Background Solid organ transplant recipients are at increased risk for developing malignancies. Polyomaviruses (PV) have been historically associated with experimental tumor development and recently described in association with renourinary malignancies in transplant patients. The aim of this study was to investigate the relationship between PV replication and smoking, and the development of malignant neoplasms in kidney transplant recipients. Methods A retrospective case-control study was conducted for PV replication in all kidney biopsies and urine cytologies performed between 1998 and 2014 from kidney transplant recipients at the University of Maryland Medical Center. Polyomavirus-positive patients (n = 943) were defined as having any of the following: a kidney biopsy with PV associated nephropathy, any urine cytology demonstrating “decoy” cells, and/or significant polyomavirus BK viremia. Polyomavirus-negative matched patients (n = 943) were defined as lacking any evidence of PV replication. The incidence of malignancy (excluding nonmelanoma skin tumors) was determined in these 1886 patients and correlated with demographic data and history of smoking. Results There was a 7.9% incidence of malignant tumors after a mean posttransplant follow-up of 7.9 ± 5.4 years. Among all cancer subtypes, only bladder carcinoma was significantly associated with PV replication. By multivariate analysis, only PV replication and smoking independently increased the risk of bladder cancer, relative risk, 11.7 (P = 0.0013) and 5.6 (P = 0.0053), respectively. Conclusions The findings in the current study indicate that kidney transplant recipients with PV replication and smoking are at particular risk to develop bladder carcinomas and support the need for long-term cancer surveillance in these patients.

Oropharyngeal cancer as a driver of racial outcome disparities in squamous cell carcinoma of the head and neck: 10‐year experience at the University of Maryland Greenebaum Cancer Center

Racial outcome disparities have been observed in head and neck squamous cell carcinoma (HNSCC) with diminished survival for black patients compared with white patients.

Automated quantification of Ki-67 proliferative index of excised neuroendocrine tumors of the lung

BackgroundThe histopathologic distinction between typical carcinoid (TC) and atypical carcinoid (AC) of the lung is based largely on mitotic index. Ki-67 may aid in separation of these tumors, as well as the distinction from large cell neuroendocrine carcinoma (LCNEC).MethodsWe identified 55 surgically resected primary neuroendocrine lung tumors (39 TC, 7 AC, 9 LCNEC) based on mitotic rate and histologic features. Ki-67 proliferative index based on automated image analysis, tumor necrosis, nodal metastases, local or distant recurrence, and survival were compared across groups.ResultsThe mean mitotic count and Ki-67 index for TC, AC, and LCNEC were 0.1 and 2.3%, 3.4 and 16.8%, and 56.1 and 81.3% respectively. The Ki-67 index did not overlap among groups, with ranges of 0-6.7% for TC, 9.9-25.7% for AC, and 63.2-91.9% for LCNEC. Nodal metastases were identified in 4/39 (10%) TC, 2/7 (22%) AC, and 2/8 (25%) LCNEC. There was no survival difference between TC and AC, but there was a significant survival difference between LCNEC and TC and AC combined (p < 0.001). There was a step-wise increase in disease free survival with tumor grade: no TC recurred, 2/7 AC recurred or progressed (median interval 35.5 months), and all LCNEC recurred or progressed (median interval 10.1 months). No patient with TC or AC died of disease, compared to 7/8 LCNEC with follow-up data.ConclusionsWe conclude that Ki-67 index is a useful diagnostic marker for neuroendocrine tumors, with 7% a divider between AC and TC, and 50% a divider between LCNEC and AC. LCNEC is biologically different from AC and TC, with a much more aggressive course, and a high Ki-67 index.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_174

Oropharyngeal cancer (OPC) drives racial outcome disparities in squamous cell carcinoma of the head and neck (HNSCC): Ten year experience at the university of maryland greenebaum cancer center (UMGCC)

Racial outcome disparities have been observed in head and neck squamous cell carcinoma (HNSCC) with diminished survival for black patients compared with white patients.

Oropharyngeal cancer as a driver of racial outcome disparities in squamous cell carcinoma of the head and neck: 10-year experience at the University of Maryland Greenebaum Cancer Center: Racial disparities in HNSCC

Racial outcome disparities have been observed in head and neck squamous cell carcinoma (HNSCC) with diminished survival for black patients compared with white patients.