Expression profile of the tumorigenic factors associated with tumor size and sex steroid hormone status in uterine leiomyomata  Jian-Jun Wei, M.D., Luis Chiriboga, Ph.D., Khush Mittal, M.D.  Fertility and Sterility  Volume 84, Issue 2, Pages 474-484 (August 2005) DOI: 10.1016/j.fertnstert.2005.01.142 Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 Differential expression and dendrogram cluster analysis of selected tumorigenic factors in uterine leiomyomata (ULM) in age groups of 36–40 (I), 41–45 (II), 46–50 (III), 51–60 (IV), and 61 years and older (V). (A) Immunoreactivity for Ki-67 (y axis shows average positive cells per tissue core) in the five age groups (x axis). (B) Dot plot analysis of patients’ age (y axis) and tumor sizes (2 cm (I), 2.1–5.0 cm (II), 5.1–8.0 cm (III), and > 8.1 cm (IV)) (x axis). Each dot represents an individual patient. (C) The average values of net gain or loss of immunoreactivity for 14 selected tumorigenic factors with marker names listed below in two age groups with their standard errors (small T-bars on top of each wide bar). *P<.05. (D) The dendrogram and hierarchic cluster analysis of 15 selected immunomarkers in 60 cases with ULM. Columns represent the immunomarkers and rows are the ULM. The immunoscores are indicated by green (downregulation), red (upregulation), black (no change), and gray (no data obtained). The cluster analysis with age scores added (green: age below average; black: mean age; red: age above average) (see methods for detail). The separated dendrograms of up- and downregulated markers are also shown. The case numbers and patients’ ages are indicated to the right. Wei. Tumorigenic factors in uterine leiomyomata. Fertil Steril 2005. Fertility and Sterility 2005 84, 474-484DOI: (10.1016/j.fertnstert.2005.01.142) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 Differential expression and dendrogram cluster analysis in the selected tumorigenic factors in uterine leiomyomata (ULM) at tumor sizes of 2 cm (I), 2.1–5 cm (II), 5.1–8 cm (III), and 8.1–19 cm (IV). (A) Immunoreactivity for Ki-67 (y axis shows average positive cells per tissue core) in the four tumor size groups (x axis). One tumor in group I showed a much higher Ki-67 score (38/core) and was not included in the analysis. (B) The average values of net gain or loss of immunoreactivity for 11 selected tumorigenic factors with marker names listed below in the four tumor size groups. (C) The mean values of seven large ULM (from a total of 126 tissue cores) and seven small ULM (from a total of 14 cores) with standard errors on top. *P<.01. (D) The dendrogram and hierarchic cluster analysis of 15 selected immunomarkers in 60 cases with ULM as shown in Figure 1D. The cluster analysis with tumor size is presented in the last column. The case numbers and tumor sizes are indicated to the right. Wei. Tumorigenic factors in uterine leiomyomata. Fertil Steril 2005. Fertility and Sterility 2005 84, 474-484DOI: (10.1016/j.fertnstert.2005.01.142) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 Differential expression and dendrogram cluster analysis in the selected tumorigenic factors in uterine leiomyomata (ULM) in different endometrial phases: proliferative/follicular phase (PE), secretory/luteal phase (SE), and inactive phase (IA). (A) The average values of net gain or loss of immunoreactivity for 14 selected tumorigenic factors with marker names were listed below in SE and PE phases. Standard errors are marked by small T-bars on each wide bar. *P<.05. (B) The dendrogram and hierarchic cluster analysis of 15 selected immunomarkers in 60 ULM as shown in Figure 1D. The cluster analysis with different endometrial phases was analyzed. The case numbers, patients’ ages, and phases are indicated to the right. Wei. Tumorigenic factors in uterine leiomyomata. Fertil Steril 2005. Fertility and Sterility 2005 84, 474-484DOI: (10.1016/j.fertnstert.2005.01.142) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions

FIGURE 4 Differential expression and dendrogram cluster analysis in the selected tumorigenic factors in uterine leiomyomata (ULM) in the absence (NM) or presence of adenomyosis (ADM). (A) The average values of net gain or loss of immunoreactivity for 14 selected tumorigenic factors with marker names are listed below in presence (blue) and absence (red) of adenomyosis. Standard errors are marked by small T-bars on each wide bar. (B) The dendrogram and hierarchic cluster analysis of 15 selected immunomarkers in 60 ULM as shown in Figure 1D. The case numbers, patients’ ages, and absence (NM) and presence (ADM) of adenomyosis are indicated to the right. Wei. Tumorigenic factors in uterine leiomyomata. Fertil Steril 2005. Fertility and Sterility 2005 84, 474-484DOI: (10.1016/j.fertnstert.2005.01.142) Copyright © 2005 American Society for Reproductive Medicine Terms and Conditions