Abstract 5020: Associations of clinical, molecular and immunohistochemical parameters in five different types of uterine smooth muscle tumors
Authors: Kanis Margaux J. , Bender Jennifer L. , Strohl Anna E. , Scholtens Denise , Liu Dachao , Lurain John , Shahabi Shohreh , Wei Jian-Jun 
Published: July 2016

Objective:

To evaluate clinical, molecular and pathologic factors associated with 5 types of uterine smooth muscle tumors.

Materials and Methods:

Seventy-nine patients with leiomyosarcoma [31 (39.2%) LMS], smooth muscle tumors of undetermined significance [10 (12.7%) STUMP], atypical leiomyoma [19 (24.1%) ALM], mitotically active leiomyoma [5 (6.3%) MALM], and cellular leiomyoma [14 (17.7%) CLM] treated from 1997-2015 were analyzed. Statistical analysis was performed using ANOVA, chi-square and logrank tests.

Results:

Mean age (years) differed across histologies: 54 (LMS), 36 (STUMP), 41 (ALM), and 47 (CLM/MALM) (p&lt;.0001). Median follow up was 37 months (range 0-226). Those with LMS were more likely to have a family history of cancer (48%, p&lt;.003). Tobacco use did not vary by histology but was significantly associated with recurrence (50 vs. 17%, p = .03). Fifty-four percent of LMS recurred and 48% died. There were no recurrences or deaths due to non-LMS histology. Patients who recurred were more likely to have a family history of malignancy (58 vs 41%, p = .0005). There was no association with recurrence or survival for: ethnicity, parity, hormone use, personal history of malignancy, tumor size or weight.

Of 6 gene markers examined by immunohistochemistry (IHC), ER and PR expression were significantly lower in LMS than in other types (p &lt;.0001). High ER IHC intensity was protective against recurrence compared to negative ER IHC (3 vs 42%, p = .0014). High PR IHC intensity was also protective against recurrence compared to negative PR IHC (3% v 56%, p &lt;.0001). Higher PFS was significantly associated with ER (p = .0019) and PR (p &lt;.0001) positivity. PR was associated with a significant increase in OS (p&lt;.0001). Ki67 index was higher in LMS than other types (p = .05). PTEN IHC intensity correlated with histology (p = .03) and a shorter PFS and OS (p = .01, p = .018, respectively). PTEN molecular analysis correlated with shorter survival (p&lt;.0001). Using an H-score cut-off of 40 for ER and 25 for PR, LMS will be positive in 21-24% of cases compared to over 80% in other histologies. Ki67 was uniquely positive in 81% of LMS tumors. P53 mutations were detected in LMS, STUMP and ALM, and absent in CLM/MALM.

Conclusions:

ER/PR and Ki67 IHC are valuable biomarkers in differentiating histology and predicting clinical recurrence in uterine smooth muscle tumors. Smoking cessation is key to decreasing recurrence.

Citation Format: Margaux J. Kanis, Jennifer L. Bender, Anna E. Strohl, Denise Scholtens, Dachao Liu, John Lurain, Shohreh Shahabi, Jian-Jun Wei. Associations of clinical, molecular and immunohistochemical parameters in five different types of uterine smooth muscle tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5020.