Image Cytometric Measurement of Nuclear Proliferation Markers (MIB-1, PCNA) in Astrocytomas:Prognostic Significance

Abstract

I m a g e C y t o m e t r i c M e a s u r e m e n t o f N u c l e a r P r o l i f e r a t i o n M a r k e r s ( M I B -1 , P C N A ) i n A s t r o c y t o m a s1 " 3 For astrocytomas, the proliferative capability of the neoplasm becomes increasingly important because of the confines of the skull and the rapidity of the onset of symptoms as the tumor enlarges. Additional insight into the behavior of astrocytomas has been gained by evaluating the proliferative activity for individual neoplasms. This approach is especially important when assessment of proliferation can overcome biopsy sampling inadequacies in which histologic criteria are not readily evident or are difficult to determine.Research into proliferation markers for astrocytomas has included several approaches, including analysis of variance showed a significant correlation between the histologic grade and MIB-1 and between the histologic grade and PCNA. The Cox Proportional Hazards Regression Model showed a statistically significant correlation between survival and MIB-1 and between survival and PCNA. Increasing proliferation correlated with shortened survival. Proliferation in astrocytomas, measured as MIB-1 and PCNA by image cytometry, correlates significantly with histologic grade and patient survival, providing useful additional information for determining the diagnosis and prognosis.

Astrocytomas and Prognosis-From Morphology to Tumor Biology

“…This is not in keeping with earlier studies which have shown that grade reliably predicts survival in astrocytoma patients [15,16]. The lack of significant difference in survival in the present study could be due to the short follow up available for most of the patients and the low numbers in Grade I and Grade III tumors.…”

“…This relation has been seen in other series with large number of cases snd utilising other proliferation markers as well [7,16,20,22,23]. The range of PCNA LI is variable, from 0.00-30.96% in some studies [20,23] to 0.1-95% in others [7,16,22]. Our range of 0.4-72% was comparable with the second group.…”

“…However, difference in survival between low PCNA LI group (25.18 months) and high PCNA LI group (9.15 months) was not significant. While a few studies say PCNA loses significance when compared in multivariate analyses to age, grade and type [23,25] several studies have shown a significant association with prognosis [16,22].…”

Whole Slide Imaging for Analytical Anatomic Pathology and Telepathology: Practical Applications Today, Promises, and Perils

“…66,67 Earlier studies from our department established the role of Ki-67 quantitation in glial neoplasms. 68,69 Recently, using multimodal, multiscale approaches and machine-based classification, researchers have devised ways to mine scanned histologic data on glioblastoma in The Cancer Genome Atlas Project and other sources; the resulting quantitative morphometric analysis findings have been further integrated with molecular data to provide in silico cancer research [70][71][72][73][74][75][76][77][78][79][80] and with radiologic data to provide clinicopathoradiologic correlation. 81 Insights from this work also include findings on the importance of tumor-infiltrating lymphocytes in glioblastoma, 72 and in silico approaches from these studies have uncovered novel findings regarding the regulation of asymmetric cell division in glioblastoma by such mediators as the human Brat ortholog TRIM3.…”

The role of apoptosis, cell proliferation index, bcl-2, and p53 in glioblastoma prognosis

“…It has been suggested that the MI of gliomas can have a predictive value in their own prognosis 6,24 . Ehrmann et al 25 demonstrated a relationship between cell proliferation (as measured by the PCNA protein expression) and the prognosis of 42 astrocytic tumors.…”