Chromatin phenotype karyometry can predict recurrence in papillary urothelial neoplasms of low malignant potential

Cell Oncol. 2007;29(1):47-58. doi: 10.1155/2007/356464.


Background: A preceding exploratory study (J. Clin. Pathol. 57(2004), 1201-1207) had shown that a karyometric assessment of nuclei from papillary urothelial neoplasms of low malignant potential (PUNLMP) revealed subtle differences in phenotype which correlated with recurrence of disease.

Aim of the study: To validate the results from the exploratory study on a larger sample size.

Materials: 93 karyometric features were analyzed on haematoxylin and eosin-stained sections from 85 cases of PUNLMP. 45 cases were from patients who had a solitary PUNLMP lesion and were disease-free during a follow-up period of at least 8 years. The other 40 were from patients with a unifocal PUNLMP, with one or more recurrences in the follow-up. A combination of the previously defined classification functions together with a new P-index derived classification method was used in an attempt to classify cases and identify a biomarker of recurrence in PUNLMP lesions.

Results: Validation was pursued by a number of separate approaches. First, the exact procedure from the exploratory study was applied to the large validation set. Second, since the discriminant function 2 of the exploratory study had been based on a small sample size, a new discriminant function was derived. The case classification showed a correct classification of 61% for non-recurrent and 74% for recurrent cases, respectively. Greater success was obtained by applying unsupervised learning technologies to take advantage of phenotypical composition (correct classification of 92%). This approach was validated by dividing the data into training and test sets with 2/3 of the cases assigned to the training sets, and 1/3 to the test sets, on a rotating basis, and validation of the classification rate was thus tested on three separate data sets by a leave-k-out process. The average correct classification was 92.8% (training set) and 84.6% (test set).

Conclusions: Our validation study detected subvisual differences in chromatin organization state between non-recurrent and recurrent PUNLMP, thus allowing a very stable method of predicting recurrence of papillary urothelial neoplasms of low malignant potential by karyometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Papillary / classification
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / pathology*
  • Cell Nucleus / metabolism
  • Chromatin / metabolism*
  • Female
  • Humans
  • Karyometry / methods
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Reproducibility of Results
  • Urologic Neoplasms / classification
  • Urologic Neoplasms / metabolism
  • Urologic Neoplasms / pathology*
  • Urothelium / metabolism
  • Urothelium / pathology*


  • Chromatin