Anatomic Abstracts

February 2004

• AMACR and diagnosis of small prostate cancer foci on needle biopsy
• Human papillomavirus-positive palatine tonsillar carcinomas in young patients
• Adjunctive HPV testing in women with select cervical cytologic abnormalities
• Risk of cervical cancer associated with intervals between cancer screenings

AMACR and diagnosis of small prostate cancer foci on needle biopsy

Expression of the alpha-methylacyl-CoA racemase (AMACR) gene recently has been demonstrated by several groups to be markedly elevated in prostate cancer cells, with little expression in benign prostate tissue. It has also been suggested as a molecular marker of prostate cancer on needle biopsy. There is scant data, however, as to the sensitivity and specificity of AMACR in the diagnosis of small foci of cancer on needle biopsy. The authors conducted a study in which 209 needle biopsies of the prostate with small foci (less than five percent of a core) of prostatic adenocarcinoma were identified. A total of 175 cases were received in consultation by one of the authors (140 from a single institution and 35 from different outside institutions)—34 cases were from the author’s hospital file. Immunohistochemistry for high-molecular-weight cytokeratin and p63 was performed in all cases to confirm the diagnosis of cancer. Only AMACR staining that was significantly stronger than that of background benign glands was considered positive; 88 percent of all cases of prostate cancer were positive for AMACR. The sensitivity varied among the different groups: 100 percent for the in-house cases, 87.1 percent for the cases from a single institution, and 80 percent for cases from different outside institutions. The mean percentage of stained glands in positive cases was 95.9 percent, with 150 (71.8 percent) cases showing 100 percent of the glands positive and 25 (12 percent) cases showing no staining. Because negative staining for basal cell markers, especially in a small focus of atypical glands, is not necessarily diagnostic of prostate cancer, positive staining for AMACR can increase the level of confidence in establishing a definitive malignant diagnosis. The sensitivity of AMACR staining, however, may vary among specimens from different pathology laboratories, possibly related to differences in fixation and processing. It is important to optimize the staining technique for each laboratory and recognize that some small cancers on needle biopsy may be AMACR negative.

Magi-Galluzzi C, Luo J, Isaacs WB, et al. Alpha-methylacyl-CoA racemase: a variably sensitive immunohistochemical marker for the diagnosis of small prostate cancer foci on needle biopsy. Am J Surg Pathol. 2003:27(8):1128–1133.

Reprints: Dr. Jonathan I. Epstein, Johns Hopkins Hospital, Dept. of Pathology, Weinberg Building, 401 N. Broadway, Room 2242, Baltimore, MD 21231; jepstein@ jhmi.edu

Human papillomavirus-positive palatine tonsillar carcinomas in young patients

The prevalence of human papillomavirus in carcinomas of the head and neck has been difficult to assess due to the variability in techniques used to identify HPV in published reports. Further, the presence of risk factors other than HPV, particularly in older patients, can confound the analysis in terms of etiopathogenesis. In this study, the authors used DNA amplification by polymerase chain-reaction to identify a short HPV DNA product in archival material from 33 cases of squamous cell carcinomas from the palatine tonsil (11), larynx (seven), and oral cavity (15) in patients younger than 40 years of age. Ten tonsillar and two laryngeal carcinomas were HPV-positive. All HPV-positive tumors were nonkeratinizing and diffusely and strongly positive for p16 antibodies, whereas the HPV-negative tumors were keratinizing and had absent/focal and weak staining (scored as negative) for p16. The group with HPV-positive tumors had higher Ki-67 and lower p53 immunostaining scores than did the other group. The authors concluded that in young patients, high-risk HPV, particularly HPV16, is strongly associated with tonsillar squamous cell carcinoma and some cases of laryngeal, but not oral, tumors.

El-Mofty SK, Lu DW. Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil, and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol. 2003;27:1463–1470.

Reprints: Dr. Samir K. El-Mofty, Washington University School of Medicine, Dept. of Pathology and Immunology, 660 S. Euclid, Campus Box 8118, St. Louis, MO 63110; elmofty@ path. wustl. edu

Adjunctive HPV testing in women with select cervical cytologic abnormalities

Although human papillomavirus testing may aid in managing low-grade abnormality on screening cervical cytology, patient compliance with repeat testing programs should be considered. To determine the effectiveness and costs of repeated Papanicolaou testing and oncogenic HPV testing for detecting cervical intraepithelial neoplasia 2 or 3, the authors conducted a randomized controlled trial of combined Pap testing and cervical HPV testing using the Hybrid Capture 1 test compared with Pap test alone. Tests were performed every six months for up to two years. The study end point was colposcopic examination performed on all women at two years or earlier if an HPV test was positive or if a Pap test showed high-grade squamous intraepithelial lesion. The authors studied 257 women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion on screening cervical cytology from 66 community family practices. The main outcome measurements were detection of histologically confirmed cervical intraepithelial neoplasia 2 or 3, fully allocated costs, and loss to followup. The authors found that Pap testing and HPV testing combined detected 11 (100 percent) of 11 cases of cervical intraepithelial neoplasia 2/3, whereas Pap test alone detected seven (63.6 percent) of these 11 cases (P=.14). Corresponding specificities were 39 (46.4 percent) of 84 and 45 (71.4 percent) of 63 (P=.005). The cost-effectiveness ratio was $4,456 (Canadian) per additional case of high-grade cervical intraepithelial neoplasia. Sixty-nine (26.8 percent) of the 257 women (24.6 percent combined group versus 29.1 percent Pap test only group; P=.41) defaulted from testing or colposcopy when referred with an abnormal result. The authors concluded that combined testing was more costly but may detect a greater number of cases of cervical intraepithelial neoplasia 2/3 than Pap test alone. Poor adherence, however, limits the usefulness of a management strategy that requires repeated followup.

Lytwyn A, Sellors JW, Mahony JB, et al. Adjunctive human papillomavirus testing in the 2-year follow-up of women with low-grade cervical cytologic abnormalities: a randomized trial and economic evaluation. Arch Pathol Lab Med. 2003;127:1169–1175.

Reprints: Michelle Howard, McMaster University, Dept. of Family Medicine, 1200 Main St. W, Room HSC-2V10, Hamilton, Ontario, L8N 3Z5, Canada; mhoward@ mcmaster.ca

Risk of cervical cancer associated with intervals between cancer screenings

associated with intervals between cancer screenings

Sawaya GF, McConnell KJ, Kulasingam SL, et al. Risk of cervical cancer associated with extending the interval between cervical-cancer screenings. N Engl J Med. 2003;349(16): 1501–1509.

Reprint information not available.