Ki-67 Is a Strong Prognostic Marker for Non Small Cell Lung Cancer When Tissue Heterogeneity Is Considered
Junya Fukuoka, Takashi Hori. Toyama University Hospital, Toyama, Japan
Background: The use of tissue microarray for biomarker validation is powerful. However, heterogeneity within certain tumors may complicate the interpretation of small core stainings. Multiple coring with biased site selection is artificial and may not be the best solution for this issue. We recently developed new technique, Spiral Array, which observes the side of thick reeled sections that enable to find whole morphology included in the one axis of paraffin sections. Using Spiral Array, we investigated prognostic significance of Ki-67 staining from the view of staining heterogeneity.
Design: One hundred cases of surgically removed lung cancer were collected. Spiral Array blocks were generated out of 100 cases using paraffin sections cut at 100 µm thick. Four µm thick sections of the array block were stained for Ki-67. Staining results in the each reel were scored for areas with lowest (LS), highest (HS), and dominant (DS) expression frequencies exclusively in the cancer cells. The scores were divided into four grades (0, <1%; 1, 1-10%; 2, 11-30%; 3, >30%). Clinical records including follow up status were collected, and prognostic significance of Ki-67 was analyzed using Log rank test.
Results: Seventy eight cases had clinical data including follow up status. Pathological stage was available for 91 patients including 43 stage IA, 22 stage IB, 2 stage IIA, 9 stage IIB, 13 stage IIIA, 1 stage IIIB, and 1 stage IV. The proportion of Ki-67 staining was 18 score 3, 28 score 2, 29 score 1, and 21 score 0. Numbers obtained by subtraction of LS from HS were considered as heterogeneity score (HeS) where more than HeS2 were seen in 23 cases. Cases with score 2 and 3 of HS and HeS showed significant poorer prognosis (both P<.001), whereas LS or DS did not show any prognostic values. The results were identical when analysis was limited to adenocarcinoma and squamous cell carcinoma. COX multivariate analysis showed that both HS and HeS to be independent of risk factors affecting overall survival.
Conclusions: Ki-67 is a strong prognostic marker for non small cell lung cancer when highest staining frequency or levels of staining heterogeneity are considered. Considering tissue heterogeneity is important for the establishment of tissue-based biomarkers.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 308, Tuesday Afternoon