CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.
Acellular mucin in rectal cancer patients showing pathologic complete response to preoperative chemoradiotherapy
Patients with locally advanced rectal adenocarcinoma who receive preoperative chemoradiotherapy occasionally show acellular mucin in resection specimens that had shown pathologic complete response, but the clinical and prognostic significance of this finding has generated controversy. The authors analyzed data from 217 consecutive patients showing pathologic complete response (pCR) to preoperative chemoradiotherapy (CRT) followed by resection to evaluate the clinicopathologic features and prognostic significance of acellular mucin. Patients were categorized according to the presence of acellular mucin, as identified by pathologic analysis. Clinicopathologic findings and oncologic results were compared. Acellular mucins were identified in 35 (16.1 percent) of 217 pCR patients. They were found predominantly in male patients (20.8 percent versus 9.8 percent; P=.039) and in those with mucinous/signet ring cell differentiation (66.7 percent versus 15.1 percent; P=.008). The presence of acellular mucin was more frequent in patients with a shorter (less than 42 days) CRT-operation interval (22.6 percent versus 10.3 percent; P=.017). With a mean followup of 41 months (range, two to 119 months), the three-year overall survival rate (96.8 percent with mucin versus 95.9 percent without mucin; P=.314) and three-year disease-free survival rate (97 percent with mucin versus 93 percent without mucin; P=.131) did not differ between the groups. The authors concluded that the presence of acellular mucin in rectal cancer patients showing pCR to preoperative CRT is associated with male gender and mucinous differentiation and does not have a significant impact on oncologic outcomes. Acellular mucins are also associated with the CRT-operation interval as a phenomenon of time-dependent response to CRT.
Lim SB, Hong SM, Yu CS, et al. Prevalence and clinical significance of acellular mucin in locally advanced rectal cancer patients showing pathologic complete response to preoperative chemoradiotherapy. Am J Surg Pathol. 2013;37(1):47–52.
Correspondence: Dr. Seok-Byung Lim sblim@amc.seoul.kr
Association between p16 expression and human papillomavirus in urinary bladder squamous cell carcinoma
Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The authors conducted a study to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by in situ hybridization at the DNA level and immunohistochemistry at the protein level. P16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma or 27 cases of urothelial carcinoma with squamous differentiation. P16 expression was detected in 13 cases (31 percent) of squamous cell carcinoma and nine cases (33 percent) of urothelial carcinoma with squamous differentiation. No correlation was found between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. The data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. P16 expression should not be used as a surrogate marker for evidence of HPV infection in squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HPV DNA nor protein is detectable in these neoplasms.
Alexander RE, Hu Y, Kum JB, et al. P16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma. Mod Pathol. 2012;25(11):1526–1533.
Correspondence: Dr. L. Cheng at liang_cheng@yahoo.com
Immunohistochemical signature comprising PTEN, MYC, and Ki-67 and disease progression in prostate cancer
Loss of the tumor suppressor PTEN is common in prostate cancer and may have prognostic significance. The authors examined PTEN and additional protein markers in primary tumors from patients with high-risk, localized prostate cancer who received adjuvant docetaxel in the prospective multicenter trial TAX2501. Fifty-six of 77 patients enrolled in TAX2501 had primary prostatectomy specimens available for immunohistochemical analysis of PTEN, MYC, ERG, tumor protein p53 (p53), antigen Ki-67 (Ki-67), and phosphorylated forms of Akt, mammalian target of rapamycin, and S6 ribosomal protein. Protocol-defined progression included a prostate-specific antigen (PSA) level of 0.4 ng/mL or greater, radiologic/clinical recurrence, or death. Univariate and multivariable proportional hazards regression analyses were used to investigate the influence of PTEN status and other protein markers on progression-free survival. In this exploratory, post hoc analysis, PTEN protein loss was observed in 61 percent of patients and was associated with lower preoperative PSA levels, higher clinical stage, lower Ki-67 expression, and the presence of p53 and ERG. In univariate analysis, the factors associated with progression-free survival included Gleason sum, seminal vesicle invasion, PTEN status, MYC expression, and Ki-67 expression. In multivariable analysis, only three variables emerged as independent prognostic factors for progression-free survival: PTEN status (P=.035), MYC expression (P=.001), and Ki-67 expression (P<.001). A prognostic model was constructed that incorporated clinical covariates as well as information on PTEN, MYC, and Ki-67. The results indicated that PTEN status, MYC expression, and Ki-67 expression in primary tumor samples may predict progression-free survival more accurately than clinical factors alone in men with high-risk prostate cancer who receive adjuvant docetaxel after prostatectomy. If validated, these hypothesis-generating findings may have prognostic and therapeutic implications and may aid clinical trial design.
Antonarakis ES, Keizman D, Zhang Z, et al. An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy. Cancer. 2012;118(24):6063–6071.
Correspondence: Dr. Mario A. Elseberger at eisenma@jhmi.edu