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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A088
Goal: To study the value of MIB-1 immunoquantitation for grading
support ad for the prediction of biological behavior of cervical intraepithelial
neoplasia.
Background: Invasive carcinoma may develop from CIN-1 lesions
while CIN-2 and CIN-3 may not progress. Since intra- and interobserver
reproducibility in grading CIN lesions is not always perfect, MIB-1 positive
nuclei (1,2) were quantified in view of a more objective classification of
CIN lesions.
Material & methods: 67 cervical biopsies (23 CIN-1, 23 CIN-2,
20 CIN-3) were assigned to CIN classes by different independent,
experienced pathologists on HE-stained sections. MIB-1 positive nuclei
were quantified in 4 micrometer thick paraffin block sections,
adjacent to the HE-sections used for CIN grading. In each case,
the lumen and basal membrane of the most severely dysplastic epithelium
was marked electronically, using a QPRODIT (version 6.1) interactive image
analysis system (Leica, Cambridge,
England) with a 40X objective. At least 75 positive nuclei were marked
interactively by the cursor. Thickness (=T) of the epithelium at the
location of the nucleus indicated, distance of the nucleus to the basal
membrane (=DBM) and to the lumen (=DL), stratification index (=DBM/T),
density of positive nuclei per 100 micrometer basal membrane, 90th percentile
of the stratification index and percentage positive nuclei in the deep
third, middle third, and upper third layer of the epithelium were determined,
followed by single- and multivariate regression analyzes with the CIN
grade as the independent variable.
Results: The percentage positive nuclei in the deepest layer of
the epithelium gives strong discrimination between CIN-1 vs CIN-2 and
CIN-1 vs CIN-3, but not between CIN-2 and CIN-3. The 90th percentile of
the stratification index is a stronger discriminator and combination with
the density of positive nuclei per 100 micrometer basal membrane is the
best discriminating set of features to distinguish the three CIN grades
at the same time.
Two CIN-1 cases were misclassified as CIN-2 or CIN-3, one of which showed
CIN-3 during follow-up. Nine of the 20 CIN-2 cases completely overlapped
with CIN-3 cases. In two of these nine cases there
was CIN-3 at some distance in the biopsy or in the history.
Conclusion: MIB-1 immunoquantitation was comparable to a
previous independent study (1). The "misclassified" low CIN grades were
often associated with high CIN grade elsewhere in the biopsy, and in the
few cases where a subsequent biopsy was taken and histologic examination
was done, with high CIN grades. This suggests that MIB-1 immunoquantitation
is a biologic indicator of progression of seemingly low grade CIN. Supported in part
by grant #98-111 of the SBDM
MIB-1 IMMUNOQUANTITATION IN CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN):
A SENSITIVE MARKER FOR GRADING AND DIFFERENTIATION OF BIOLOGIC
UNFAVORABLE CIN-CASES
Kruse AJ, Broeckaert M, Baak JPA
Departments of Pathology, Free University Hospital, Amsterdam and Medical
Center Alkmaar, Netherlands
References:
1) Bulten J. et al. J. Pathol. 1996; 178:268-273
2) Mc Cluggage W.G. Int. J. Gynaec. Pathol. 1996; 131-136
3) Van Hoeven van K.H. Int. J. Gynaec. Pathol. 1997; 16:15-21