Spatial differences in biologic activity of large uterine leiomyomata Jian-Jun Wei, M.D., Xing-Min Zhang, M.D., Luis Chiriboga, Ph.D., Herman Yee, M.D., Ph.D, Mary A. Perle, Ph.D., Khush Mittal, M.D.  Fertility and Sterility  Volume 85, Issue 1, Pages 179-187 (January 2006) DOI: 10.1016/j.fertnstert.2005.07.1294 Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 Scheme diagram of the tissue microarray preparation from three-dimensional tumor sections in the large uterine leiomyomata (ULM). (A) Tissue sections were dissected from 3 axes (X, Y, and Z) and 6 zones (from center to periphery). (B) H&E-stained slides from each tissue section were reviewed and tissue cores taken and arrayed on a recipient block (C). (D) Some examples of immunoreactivity for Factor VIII (F8) and VEGF in large ULM (zones 1 to 6), myometrium (MM), and small ULM (S-ULM). Wei. Spatial differences in large leiomyomata. Fertil Steril 2006. Fertility and Sterility 2006 85, 179-187DOI: (10.1016/j.fertnstert.2005.07.1294) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 Differential expression of ER and PR in large (L-ULM) and small (S-ULM) ULM. (A) The levels of ER (dashed line) and PR (solid line) expression in L-ULM (from zone 1 to zone 6) and in S-ULM. The baseline of ER/PR values in myometrium (MM) is set as zero. (B) The mean scores of ER and PR in S-ULM and L-ULM. The standard errors are indicated as vertical T bars. *P<.05. Wei. Spatial differences in large leiomyomata. Fertil Steril 2006. Fertility and Sterility 2006 85, 179-187DOI: (10.1016/j.fertnstert.2005.07.1294) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 Spatially differential expression of GCR and MIB1 (left panel) and CD24, EGFR, IGF1R, HMGA2, RXR, IGF2, and Bcl2 (right panel) in the large ULM (from zone 1 to zone 6) in comparison to small ULM (S-ULM). The baselines in myometrium (MM) for each marker are set as zero. The standard errors for GCR and MIB1 are given as vertical T bars. *P<.05. Wei. Spatial differences in large leiomyomata. Fertil Steril 2006. Fertility and Sterility 2006 85, 179-187DOI: (10.1016/j.fertnstert.2005.07.1294) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 4 Spatial distribution of the vessel density (A) and percentage of hyaline degeneration (B) in large ULM (from zone 1 to zone 6) and in small ULM (S-ULM). The baselines of the vessel density and hyalinization in myometrium (MM) are set as zero. *P<.05. Wei. Spatial differences in large leiomyomata. Fertil Steril 2006. Fertility and Sterility 2006 85, 179-187DOI: (10.1016/j.fertnstert.2005.07.1294) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 5 Spatially differential expression of VEGF (solid line) and HIF1 (dashed line) in the large ULM (from zone 1 to zone 6) and in small ULM (S-ULM). The baselines of VEGF and HIF1 values in myometrium (MM) are set as zero. The standard errors were given as vertical T bars. *(P<.05); **(P<.01). Wei. Spatial differences in large leiomyomata. Fertil Steril 2006. Fertility and Sterility 2006 85, 179-187DOI: (10.1016/j.fertnstert.2005.07.1294) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 6 Spatially differential expression of the selected gene products (listed on the right) in large uterine leiomyosarcomas (LMS) (from zone 1 to zone 6) and matched small ULM (S-ULM). The baselines for each marker value in myometrium (MM) are set as zero. Wei. Spatial differences in large leiomyomata. Fertil Steril 2006. Fertility and Sterility 2006 85, 179-187DOI: (10.1016/j.fertnstert.2005.07.1294) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 7 Differential expression of the gene products (indicated below the bars), vessel density, and hyaline degeneration between the large ULM (L-ULM) and small (S-ULM) ULM. The standard errors are shown as vertical T bars. *P<.05. Wei. Spatial differences in large leiomyomata. Fertil Steril 2006. Fertility and Sterility 2006 85, 179-187DOI: (10.1016/j.fertnstert.2005.07.1294) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions