Dual immunostaining of cervical cytology specimens with atypical squamous cells for p16/Ki-67 does not exclude the existence of a high-grade squamous intraepithelial lesion

This study was conducted to evaluate the accuracy of p16/Ki-67 dual immunostaining compared to high-risk human papillomavirus (HR-HPV) DNA testing for cervical intraepithelial neoplasia (CIN) in women with atypical squamous cells, cytology not excluding high-grade squamous intraepithelial lesion (ASC-H). Data were collected from 73 patients diagnosed to have ASC-H on a Pap smear who were HPV genotyped and had histological examination of a cervical biopsy. The CINtec®PLUS kit was used on residual liquid-based material, and the immunoreactivity of dual-stained cells was graded according to the number as follows: G1 (1–5 positive cells), G2 (6–10), G3 (11–20), and G4 (> 20). Accuracy was evaluated based on the histological examination of colposcopy-guided biopsy or cervical conization on follow-up. Of the 70 patients with available data, positive p16/Ki-67 was associated with histological severity as follows: 15 % in negative histology, 67 % in CIN 1, 90 % in CIN 2, and 100 % in CIN 3. The average grade of positive p16/Ki-67 staining also increased from 0.2 in histologically negative cases to 1.2 in CIN 1, 2.4 in CIN 2, and 2.9 in CIN 3 (p?<?0.01). For patients with CIN 2 or higher, p16/Ki-67 had a sensitivity of 94.6 % and a specificity of 75.8 %, while HR-HPV testing showed a sensitivity of 67.6 % and a specificity of 66.7 %. p16/Ki-67 immunostaining demonstrated better accuracy than HR-HPV for detecting CIN 2 or higher in patients with ASC-H cytology. Given the higher concordance with histological diagnosis, the grading system of positive p16/Ki-67 can be a useful adjunct for predicting high-grade lesions in clinical practice.     

Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma

Jang K‐S, Song Y S, Jang S‐H, Min K‐W, Na W, Jang S M, Jun Y J, Lee K H, Choi D & Paik S S
(2010) Histopathology 56, 229–239 Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma Aims: Tumour suppressor phosphatase and tensin homologue (PTEN) is an important negative regulator for the PIP3/Akt signalling pathway that promotes cell proliferation and inhibits apoptosis. Inactivation of PTEN by mutation, deletion and promoter hypermethylation has been demonstrated in a range of cancers. The aim was to investigate whether the loss of nuclear PTEN protein expression correlates with conventional clinicopathological parameters and patient survival. Methods and results: Immunohistochemistry staining for PTEN was performed on a tissue microarray of 19 samples of normal colonic mucosa, 14 adenomatous polyps, 482 adenocarcinomas and 56 metastatic lymph nodes. All 19 normal colonic mucosa samples (100%) were positive and 12 (85.7%) out of 14 adenomatous polyps were positive for PTEN. However, only 241 (50.0%) of the 482 colorectal adenocarcinomas and 26 (46.4%) of the 56 metastatic lymph nodes were positive for PTEN. Loss of PTEN expression was related to defective mismatch repair protein expression and colonic localization rather than rectal localization. On univariate survival analysis, patients with PTEN? adenocarcinoma revealed a poor overall and disease‐free survival (P = 0.030 and P = 0.046, respectively). On multivariate analysis, a significant difference was observed in patients with stage II cancer that was not observed in other stages. Conclusions: Nuclear PTEN expression gradually decrease during the normal–adenoma–adenocarcinoma–metastasis sequence, which suggests an important role for PTEN in carcinogenesis. Moreover, loss of nuclear PTEN expression was a marker of poor clinical outcome in patients with stage II colorectal cancer.     

Prognostic value of immunohistochemical staining of p53, bcl-2, and Ki-67 in small cell lung cancer

Small cell lung cancer (SCLC) is one of the most fatal cancers in humans and many factors are known to be related to its poor prognosis. Immunohistochemical (IHC) stainings were done on SCLC specimens in order to investigate the prognostic value of the apoptosis-related gene expression and the tumor proliferative maker, and the relationships among these IHC results and patients clinical characteristics, chemoresponsiveness, and survival were analyzed. The medical records of 107 patients were reviewed retrospectively. IHC stainings for p53, bcl-2 and Ki-67 expressions were performed in the 66 paraffin-embedded biopsy samples. Sixty-six out of the 107 patients were evaluable for response rate and survival. The overall response rate was 75% (95% Confidence Interval=74-76%) and the median survival time was 14 months. The median survival time of limited stage was 16 months and that of extensive stage was 10 months. The prevalence of p53, bcl-2 and Ki-67 expression was 62%, 70%, and 49%, respectively. There were no correlations among the immunoreactivities of p53, bcl-2 and Ki-67 with clinical stage, chemoresponsiveness or overall survival. The clinical stage was the only prognostic factor influencing survival. The expression rates of p53, bcl-2, and Ki-67 were relatively high in SCLC without any prognostic significance. The exact clinical role of these markers should be defined through further investigations.     

Subject Index to Volume 23

Subject Index

Subject Index to Volume 23     

Transfected MCF-7 cells as a model for breast cancer progression

Summary The MCF-7 human breast carcinoma cell line has been used as a recipient for eukaryotic plasmid expression vectors to determine the effects of growth factor and growth factor receptor overexpression on the estrogen-dependent, antiestrogen sensitive and poorly metastatic phenotypes exhibited by this line. Overexpression of some members of the erbB family of ligands and receptors were found to have some effects on these pheno-types. However, only when two members of the fibroblast growth factor family, FGF-1 and FGF-4, were overexpressed was progressivein vivo growth observed is either ovariectomized nude mice without estrogen supplementation or in mice that received tamoxifen treatment. FGF transfected cells also exhibited an increased ability to form micrometastases. The implications of these results with regard to the possible role of the paracrine and autocrine effects of angiogenic growth factor production in breast cancer progression are discussed.     

Inhibitory effects of retinoids on development of squamous metaplasia in rat mammary epithelial organoids cultured in Matrigel

Squamous metaplasia (SQM) developed in cultures of rat mammary organoids in reconstituted basement membrane, Matrigel, under either a complete hormone medium (CHM) or a serum-free mammary epithelium growth medium (MEGM). Organoids cultured in CHM gave rise to fewer such SQM (˜5%) than those in MEGM (˜16%). Formation of SQM was completely suppressed when retinoids were added to CHM. However, a few SQM were still observed in cultures in MEGM with added retinoids. Addition of 5% fetal bovine serum suppressed development of SQM cultured in MEGM. Delayed addition of retinoids also inhibited further development of SQM. Development of SQM from mammary epithelial cells is not common, and regulatory molecules other than retinoids apparently are involved in their formation and prevention.     

Development of a sampling and analytical method for 2,2-dichloro-1,1,1-trifluoroethane in workplace air

The use of 2,2-dichloro-1,1,1-trifluoroethane (compound number: HCFC-123) is growing in industry as a substitute for ozone-depleting chlorofluorocarbons (CFCs). Recently, liver-related illnesses have been reported from industries handling HCFC-123. However, information on worker exposure to the material is limited, and an acceptable sampling/analytical method is not available. The aim of this study was to develop a widely applicable sampling and analytical method to determine worker exposures to airborne HCFC-123 and to evaluate the performance of the method. A solid sorbent tube, containing two sections (400 mg in the front and 200 mg in the back) of activated coconut-shell charcoal was chosen for sampling airborne HCFC-123 vapor. The breakthrough volumes were 13.6 L at 3597 +/- 210.1 ppm (with a sampling airflow rate of 0.046 L/min) and 17.0 L at 1841 +/- 4.5 ppm (with sampling airflow rate of 0.046-0.050 L/min). Samples of HCFC-123 in the charcoal tube were stable for 7 days either at room temperature or in a refrigerator and a migration occurred within 14 days at room temperature. It is recommended that the HCFC-123 sample in activated charcoal tubes be stored either at room temperature or in a refrigerator and be analyzed within 7 days. The HCFC-123 in the charcoal tubes was desorbed into dichloromethane and analyzed using gas chromatography/ flame ionization detection. The limit of detection was 0.23 mg/sample, and the average desorption efficiency was 99.0%. The total coefficient of variation was 0.060, and the method accuracy was 16.6%. In conclusion, the performance of the sampling and analytical method developed for the determination of airborne HCFC-123 concentrations was acceptable to the NIOSH sampling and analytical criteria.