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February 2004
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.
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