Role of morphometry and proliferative parameters in grading of urothelial neoplasms.
BACKGROUND
Mean nuclear area of 10 nuclei (MNA-10), mitotic activity index (MAI) and Ki-67 are highly reproducible and can be routinely used as adjuncts to histopathological grading in classifying tumors. Assays of these biomarkers are non-invasive, rapid, easy to perform, more objective and accurate, with high sensitivity and specificity, and correlate well with tumor grade.


METHODS
This study was conducted at the Department of Pathology PGIMS, Rohtak on 50 cases, of which 25 cases were high-grade, 15 low-grade, 6 Papillary Urothelial Neoplasm of Low Malignant Potentialand 4 reactive lesions as per the 2004 ISUP/WHO classification. MNA-10, MAI and Ki-67 immunoquantitation were performed on stained sections.


RESULTS
The age of the patients varied from 35 to 87 years. Male: female ratio was 3.5:1. The mean MNA-10 (μm(2)) for High Grade Malignant Potential was 104.52 ±25.64 μm(2), which was significantly higher than in PUNLMP (47.64 ±10.23) and LMP (51.57 ±15.66). MAI (/10 HPF) showed an increasing trend from reactive lesions to HMP, with a mean of (3 ±1.16)/10 HPF to (21.36 ±5.31)/10 HPF respectively. Ki-67 labelling index, a proliferative marker, revealed increasing trend lowest with reactive lesions (10 ±2.83%) and highest in high grade tumors (65.96 ±14.44). Spearman's correlation showed maximum correlation between MAI and Ki-67 and the increasing grade of tumor.


CONCLUSIONS
MNA-10 in combination with Ki-67 and MAI was found to be stronger than MNA-10 alone. MAI has high reproducibility in differentiating low and high grade, with simple assessment in paraffin embedded sections allowing adequate histopathological analysis and visualization of proliferating cells simultaneously. This multivariate grading model should be applied in routine grading to overcome interobserver variability and to increase reproducibility of grading.
Pt.B.D. Sharma Institute of Medical Sciences, Rohtak, Haryana, India.
Monika
M
Sangwan
Pt.B.D. Sharma Institute of Medical Sciences, Rohtak, Haryana, India.
Sunita
S
Singh
Pt.B.D. Sharma Institute of Medical Sciences, Rohtak, Haryana, India.
Santosh
S
Kumar
Pt.B.D. Sharma Institute of Medical Sciences, Rohtak, Haryana, India.
Sonia
S
Chabbra
Pt.B.D. Sharma Institute of Medical Sciences, Rohtak, Haryana, India.
Rajeev
R
Sen
Govt. Medical College for Women, Khanpur Kalan, Sonipat, Haryana, India.
Praveen
P
Rana
Pt.B.D. Sharma Institute of Medical Sciences, Rohtak, Haryana, India.
Shivani
S
Malik
Pt.B.D. Sharma Institute of Medical Sciences, Rohtak, Haryana, India.
Sonia
S
Singh
Community Health Centre, Kiloi, Rohtak, Haryana, India.
Ramesh
R
Lamba
mitotic activity index; morphometry; proliferative parameters; urothelial tumors