Limits...
HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy.

McAlpine JN, Wiegand KC, Vang R, Ronnett BM, Adamiak A, Köbel M, Kalloger SE, Swenerton KD, Huntsman DG, Gilks CB, Miller DM - BMC Cancer (2009)

Bottom Line: HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence.HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance.Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gynaecology and Obstetrics, University of British Columbia, Vancouver, BC, Canada. jessica.mcalpine@vch.ca

ABSTRACT

Background: The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer.

Methods: HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy.

Results: Amplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy.

Conclusion: HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.

Show MeSH

Related in: MedlinePlus

Flowchart outlining the process of case identification for our retrospective series of mucinous ovarian cancers and mucinous borderline ovarian tumors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2803495&req=5

Figure 1: Flowchart outlining the process of case identification for our retrospective series of mucinous ovarian cancers and mucinous borderline ovarian tumors.

Mentions: Immunostaining and FISH data were available for 33 cases of mucinous carcinoma and 16 cases of mucinous BOT (Figure 1). Loss of cases from the original pool of 40 carcinomas was primarily due to use of tissue microarrays where small sample size with few tumor cells or loss of tissue after digestion result in inability to assess amplification [39]. Demographic and clinicopathologic data for the mucinous carcinomas with and without HER2 amplification are shown in Table 1. Tumor grade was the only parameter shown to be associated with progression free (PFS) (p < 0.001) and overall survival (OS) time (p < 0.001). HER2 overexpression by IHC was seen in five of the carcinomas (3+ in four cases, 2+ in one case). There was high-level HER2 amplification (HER2/CEP17 ratios > 5) in six cancer cases (6/33 = 18.2%), including the five cases with HER2 overexpression. However, one case had discordant IHC and FISH results (IHC score of 0, FISH HER2/CEP ratio of 6.7) (Table 2). Of sixteen mucinous borderline tumors, three (3/16 = 18.8%) demonstrated HER2 amplification (HER2/CEP17 ratios of 3.1-3.3). One case of BOT showed discordant results with an IHC score of 0 and HER2/CEP ratio of 2.4 (Table 3).


HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy.

McAlpine JN, Wiegand KC, Vang R, Ronnett BM, Adamiak A, Köbel M, Kalloger SE, Swenerton KD, Huntsman DG, Gilks CB, Miller DM - BMC Cancer (2009)

Flowchart outlining the process of case identification for our retrospective series of mucinous ovarian cancers and mucinous borderline ovarian tumors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803495&req=5

Figure 1: Flowchart outlining the process of case identification for our retrospective series of mucinous ovarian cancers and mucinous borderline ovarian tumors.
Mentions: Immunostaining and FISH data were available for 33 cases of mucinous carcinoma and 16 cases of mucinous BOT (Figure 1). Loss of cases from the original pool of 40 carcinomas was primarily due to use of tissue microarrays where small sample size with few tumor cells or loss of tissue after digestion result in inability to assess amplification [39]. Demographic and clinicopathologic data for the mucinous carcinomas with and without HER2 amplification are shown in Table 1. Tumor grade was the only parameter shown to be associated with progression free (PFS) (p < 0.001) and overall survival (OS) time (p < 0.001). HER2 overexpression by IHC was seen in five of the carcinomas (3+ in four cases, 2+ in one case). There was high-level HER2 amplification (HER2/CEP17 ratios > 5) in six cancer cases (6/33 = 18.2%), including the five cases with HER2 overexpression. However, one case had discordant IHC and FISH results (IHC score of 0, FISH HER2/CEP ratio of 6.7) (Table 2). Of sixteen mucinous borderline tumors, three (3/16 = 18.8%) demonstrated HER2 amplification (HER2/CEP17 ratios of 3.1-3.3). One case of BOT showed discordant results with an IHC score of 0 and HER2/CEP ratio of 2.4 (Table 3).

Bottom Line: HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence.HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance.Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gynaecology and Obstetrics, University of British Columbia, Vancouver, BC, Canada. jessica.mcalpine@vch.ca

ABSTRACT

Background: The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer.

Methods: HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy.

Results: Amplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy.

Conclusion: HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.

Show MeSH
Related in: MedlinePlus