Nuclear morphometry in ductal breast carcinoma with correlation to cell proliferative activity and prognosis

Abstract EN

Background and objectives : Morphometric is the quantitative description of biologic structures.

This study was designed to evaluate the efficiency of morphometric measurements in diagnosis and prognosis of patients with breast carcinoma.

Methods : Histological samples from 61 patients of invasive duct carcinoma (IDC) of no special type (NST), 12 cases of ductal carcinoma in situ (DCIS) and 14 control breast samples taken from fibrocystic change disease were retrospectively analyzed by computerized nuclear morphometric.

All IDC patients underwent modified radical mastectomy without preoperative chemotherapy.

The mean follow up was 28 ± 19 months (range 1-71).

In each case, 25-50 nuclei were measured and the mean nuclear area (MNA), mean nuclear perimeter (MNP), mean maximum nuclear diameter (MMND) and mean minimal nuclear diameter (Mmnd) were measured.

The mean axis ratio (MAR), mean nuclear compactness (MNC), mean nuclear size (MNS) and mean shape factor (MSHF), were calculated mathematically.

To measure the nuclear diameters, a new method was employed using the AutoCAD program.

Morphometric parameters were compared with different clinic pathologic features, patient's survival and cell proliferative activity as determined by Ki-67 immunostain-ing which was evaluated quantitatively.

Results : most of the morphometric parameters were significantly higher in DCIS and IDC groups than benign one.

In IDC group morphometric features related to nuclear size (MNA, MNP, MMND, and Mind & MNS) were significantly correlated to most clinic pathologic features and cell proliferative activity assessed by Ki-67 immunostain-ing.

However, the shape factor failed to achieve this correlation.

The univariate analysis using Kaplan Meier curves indicated that short survival time was correlated with high nuclear morphometric values (MNA, MNP, MMND, Mind, MNS and MSHF).

Moreover, the Spearman correlation analysis showed that Mind has the highest converse correlation with survival (r = -0.75, p < 0.0001).

In multivariate analysis using the stepwise Cox regression, the Mind (p = 0.002, r = 0.25) and histological grade (p = 0.009, r = 0.20) were the independent prognostic factors.

Conclusions: Our results indicate that nuclear morphometric parameters can identify an aggressive tumor phenotype and provide additional significant prognostic information in predicting survival and tumors at risk of progression.

The mean minimal nuclear diameter (6.60 mm) might be applied as quantitative criteria for nuclear grading that separate patients into two groups with good and poor prognosis.

The measurement of various nuclear parameters would be helpful in future application of automated diagnosis and grading of breast carcinoma.