Growth fraction determination in pulmonary hypoplasia using Ki-67 (MIB-1) antibody

Pulmonary hypoplasia (PH) is a developmental abnormality that is typically assessed using lung/body weight ratios, radial alveolar counts, or lung volume measurements. Although it is often assumed that PH results from failure of growth and development, analysis of the proliferative index in PH has not been extensively described. We examined the lungs of 12 fetuses and newborn infants with pulmonary hypoplasia and those of 8 gestational age-matched controls using Ki-67 immunohistochemistry. Formalin-fixed, paraffin-embedded tissues were utilized. Growth fractions (GFs) were determined for peripheral lung parenchyma and bronchioles. The ratio of GFs for parenchyma and bronchioles was compared. There was no significant difference in the GF ratios obtained between control and hypoplastic lungs when gestational age was <24 weeks. However, for gestational age > 24 weeks the GF ratio of mean values for controls was approximately four times the ratio of the mean values for the hypoplastic lungs. GF did not vary according to the presumed cause of PH, and at gestational ages <24 weeks rates were the same as or greater than those of controls. These findings suggest that proliferative potential exists at <24 weeks and that the growth of the lung parenchyma in relation to the conducting airways is significantly reduced or ceases after this point in gestation. Clinical interventions at or before 24 weeks of gestation might result in improved survival of infants with a propensity for pulmonary hypoplasia.