mtm's P16/Ki-67 Dual Immuno-Staining Identifies High-Grade Cervical Disease In ASC-US And LSIL With High Sensitivity And Specificity

mtm laboratories, a privately held diagnostics company developing, manufacturing and globally commercializing in vitro diagnostics for cervical cancer early detection and diagnosis, today announced the publication of a new paper showing that dual staining for p16 and Ki-67 can pinpoint the underlying high-grade cervical disease with a high degree of sensitivity and specificity in women with ASC-US or LSIL cytology results. These are a group of patients currently poorly served by existing screening technologies, with too many referred for unnecessary colposcopy. The paper, which details the EEMAPS study results, has been published electronically in Cancer Cytopathology on March 25, 2011 ahead of print.


The EEMAPS study used the advanced biomarker combination CINtec® PLUS, which was launched by mtm in early 2010 in Europe. Residual materials from a previous pan-European retrospective cytology study were used to prepare additional slides for p16 and Ki-67 dual immuno-staining. In total, 361 ASC-US and 415 LSIL cases with corresponding biopsy results and HPV test results were available for dual stain cytology analysis. The presence of one or more dual-stained cervical epithelial cell(s) defined a positive test result with CINtec® PLUS, independent from morphology interpretation. The clinical results showed that the sensitivity of the dual stain for high-grade disease was 92.2% (71/77) for ASC-US, and 94.2% (129/137) for LSIL cases, which is equivalent to the sensitivity results obtained for HPV testing. However, specificity was significantly higher for CINtec® PLUS as compared to HPV testing; 80.6% vs. 36.3% for ASC-US and 68.0% vs. 19.1% for LSIL.


"mtm's CINtec® PLUS is the first test that provides high sensitivity and high specificity for underlying high-grade cervical disease in a single product, irrespective of women's age and the individual HR-HPV genotype," commented Bob Silverman, CEO of mtm laboratories. "Because the test can pinpoint which women are most likely to have cervical disease and need follow up, this should reduce a large number of the unnecessary, uncomfortable and costly colposcopies carried out on women with ASC-US or LSIL."


ASC-US and LSIL are definitions for equivocal and mild to moderate abnormal cytology findings on Pap tests, and may represent 5-8% of all cervical cytology cases. While most of these findings are negative for high-grade disease, 15-20% of LSIL and 6-10% of ASC-US will harbour high-grade disease. Together, these two categories of cytology represent the source for about 60% of all cases of high-grade cervical disease in women. Unfortunately, these Pap cytology results are not adequate predictors in determining which ASC-US or LSIL cases require intervention due to the low rates of underlying disease. Adjunctive HPV testing also has limitations due to unsatisfactory specificity.


The title of the publication and the authors are as follows:















Schmidt D, Bergeron C, Denton KJ, Ridder R, for the European CINtec Cytology Study Group. p16/Ki-67 Dual-Stain Cytology in the Triage of ASCUS and LSIL Papanicolaou Cytology. Cancer Cytopathol (2011); 119, DOI: 10.1002/cncy.20140


Notes


CINtec® PLUS


CINtec® PLUS is a screening and diagnostic tool combining high sensitivity and high specificity for detecting high-grade cervical disease in a single test. The CINtec® PLUS kit detects and stains for two biomarkers: the multiply validated cell cycle regulatory protein p16INK4a (p16) and Ki-67, a marker of active cell proliferation. Clinical trials involving over 32,000 women have demonstrated that when used together, this biomarker combination is both highly sensitive and highly specific to identify those women most likely to have existing high-grade disease. Moreover, the CINtec® PLUS test is independent of age and HR-HPV type of infection.


Applied in combination the co-detection of p16 plus Ki-67 in the same cell serves as an indicator of cell cycle de-regulation that occurs during HR-HPV induced oncogenic transformation and provides an objective criterion to identify those women who are likely to harbour high-grade disease. CINtec® PLUS can be applied on conventional and liquid based cytology slides. Double immuno-reactive (or: Dual-stained) cells in cytology are positively stained for both proteins:


- Brown cellular staining indicates p16 over-expression

- Red nuclear staining indicates Ki-67 expression


Classification of Cervical Cytology


The Pap smear classifications are related to the nature of the cells sampled from the cervix showing single cells or groups of cells. The most recent classification is the Bethesda system, which divides the results of the morphologic interpretation into four main groups:


1) Cervical specimens negative for intra-epithelial lesions or malignancies (NILM) - cases with morphological interpretation within normal limits


2) Atypical Squamous Cells of Undetermined Significance (ASC-US) - cases with no definitive cellular abnormality but enough suspicion to keep the case from being considered "normal" (this is an ambiguous category)


3) Low-grade Squamous Intraepithelial Lesion (LSIL)


4) High-grade Squamous Intraepithelial Lesion (HSIL)


Broadly speaking LSIL corresponds to mild to moderate pre-cancerous disease and HSIL corresponds to high-grade pre-cancerous disease. Screening with cytology provides an indicator to the physician that something may be wrong with a woman's cervix and can be used to direct this patient towards further evaluation (eg colposcopy).


Source:

mtm laboratories AG

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