The primary goal of this study was to compare the clinical performance of an optimized and rigorously controlled immunocytochemical (ICC) assay for p16(INK4a) to high-risk (HR) human papillomavirus ...(HPV) detection by polymerase chain reaction (PCR) as diagnostic adjuncts for cytology specimens from colposcopy patients.
: The study included 403 cervical cytology specimens collected within 3 months of colposcopy. The colposcopic impression and cervical biopsy diagnosis served as the standards for correlation with cytological, p16(INK4a), and HPV data. p16(INK4a) was evaluated using an immunoperoxidase-based assay that was linear over 4 logs for the detection of HeLa-spiked positive control cytology specimens, using a threshold for positive test results that was based on receiver operating characteristic curve analysis. HR-HPV was detected by multiplex PCR using genotype-specific primers.
: In all combined diagnostic categories (negative for intraepithelial lesion and malignancy, atypical glandular cells, atypical squamous cells of undetermined significance, atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion), the p16(INK4a) ICC and HR-HPV assays, respectively, had sensitivity of 81.7% and 83.3% (P = .81) and specificity of 78.1% and 50.9% (P < .001) for the detection of underlying > or =grade 2 cervical intraepithelial neoplasia (CIN) lesions on biopsy. Furthermore, the positive predictive value of p16(INK4a) ICC was greater than that of HR-HPV for patients with biopsies > or =CIN-2 (41.2% and 24.2%, respectively, P = .001).
: This p16(INK4a) immunocytochemical assay has superior specificity but similar sensitivity to HR-HPV testing to predict underlying high-grade dysplastic lesions in patients who are referred for colposcopy. The determination of the overall performance characteristics of p16(INK4a) immunocytochemistry, as an independent test or in combination with HPV testing in low-risk screening populations, however, will require subsequent large-scale prospective clinical trials.
Prostate biopsies are usually taken from the peripheral rather than anterior region of the prostate. Consequently, tumors originating from the anterior apical region and transition zones may be ...under-sampled. We examined whether addition of transrectal anterior biopsy (TAB) would improve efficacy of prostate biopsies.
Simulations of TAB and sextant biopsy (SB) were performed using computer models of 86 autopsy prostates (AP) and 40 radical prostatectomy (RP) specimens. TAB was obtained bilaterally from apex, mid, and base regions by advancing the biopsy needle 5 mm-35 mm beyond the prostatic capsule. A phase I clinical trial with 114 patients was conducted to determine the performance of an extended biopsy protocol consisting of TAB, SB, and laterally-directed biopsy (LDB).
The overall cancer detection rates of SB and TAB were 33% and 55% for AP series (p = 0.00003); 60% and 88% for RP series (p = 0.006). Alternatively, SB + bilateral apical TAB and SB + bilateral mid TAB had cancer detection rates of 45% and 42% for AP series; 80% and 78% for RP series. The extended biopsy protocol detected cancer in 33% (38/114) of patients with 29, 25, and 15 diagnosed by SB, LDB, and bilateral apical TAB, respectively. Patients diagnosed by bilateral apical TAB versus SB (p = 0.01) and LDB (p = 0.02) were statistically significant. Without bilateral apical TAB, the overall cancer detection rate decreased to 30% (34/114).
Inclusion of bilateral TAB from apical region for first time and repeat prostate biopsies may increase diagnosis of prostate cancer. The clinical significance of these findings needs further investigations and clinical follow up.
We demonstrated in 2011 that 61% of men with postoperative PSA failure had some cribriform pattern of prostate cancer, versus 16% of nonfailures ( OR = 5.89 , P<.0001). That study used digitized ...radical prostatectomy slides from 153 men, 76 failures (≥0.2 ng/mL) matched to 77 nonfailures. The current study's hypothesis: pseudolumen size and shape variability could stratify outcome within histologic patterns (single separate acini, separate acini with undulating lumens, fused small acini, papillary, cribriform). Pseudolumens were filled digitally on image captures from previously annotated specimens. Among all 5 patterns, pseudolumen spaces averaged smaller in failures than nonfailures. After multivariate analysis controlling for stage, age, margin, cancer amount, prostate volume, and presence of individual cells (grade 5), this retained significance only for the undulating-lumens and papillary patterns. In undulating-lumens pattern, PSA failures had smaller mean pseudolumen space sizes (P=.03) but larger perimeters (P=.04), implying more pseudolumen irregularity. In papillary pattern, the number of pseudolumen spaces was higher in failures (P=.015), space size was smaller (P=.11), perimeters were smaller (P=.04), and perimeter/size ratio was higher (P=.02). In conclusion, digitally measured pseudolumen size and shape may associate with outcome.
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