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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.

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HER2 immunostaining and FISH of tumors from cases 1 and 2 (Case 2-sample from lung), who subsequently received trastuzumab either alone or in combination with conventional chemotherapy. Each tumor shows strong immunoreactivity for HER2 and amplification by FISH (HER2 probe -- red, CEP17 probe -- green).
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Figure 3: HER2 immunostaining and FISH of tumors from cases 1 and 2 (Case 2-sample from lung), who subsequently received trastuzumab either alone or in combination with conventional chemotherapy. Each tumor shows strong immunoreactivity for HER2 and amplification by FISH (HER2 probe -- red, CEP17 probe -- green).

Mentions: The first patient with recurrent mucinous carcinoma initially presented at age 19 with irregular periods, pelvic pain, increased abdominal girth, and an elevated CA125 of 110 kU/L (other markers normal). Imaging revealed a 15 cm mass and ascites. She underwent surgical staging including unilateral salpingoophorectomy (USO), appendectomy, omentectomy, peritoneal biopsies, and washings. Pathology reported a 20 × 15 × 14 cm mucinous BOT, intestinal type with focal inatraepithelial carcinoma of the ovary, all other specimens negative, stage Ia. She was observed and did well until 15 months later when she was noted to have an elevation in her CA125 to 81 kU/L. A CT scan revealed ascites and a mass in the contralateral ovary. She underwent USO and multiple biopsies. Pathology showed a mucinous borderline tumor of the ovary with intraepithelial carcinoma, but there were now implants of invasive mucinous carcinoma on the peritoneal surfaces. She received carboplatin and paclitaxel (CP) for six cycles, with normal CA125 throughout but again recurred four months after completion of therapy, based on reaccumulation of ascites, omental disease, elevated CA125 (130 kU/L), and abdominal symptoms. Pathology review of her first recurrence was performed to assess for molecular markers. This revealed the overexpression and amplification of HER2 (IHC 3+, HER2/CEP ratio 7.2) (Figure 3) and trastuzumab (6 mg/kg) was given in addition to single agent monthly carboplatin (600 mg/m2). A dramatic response, based on imaging and tumor markers, was noted after three cycles (Figure 4) and she completed a total of six cycles of this combination. She then received trastuzumab alone for three cycles with stable disease after which her markers began to rise and ascites and omental disease were seen on CT scan. Carboplatin was reintroduced but her markers continued to increase and she was changed to gemcitabine in combination with trastuzumab. Her CA125 level dropped from 1800 to 180 kU/L after the first cycle but she developed signs and symptoms of large bowel obstruction. She was taken to surgery for necrotic tumor in her cecum and splenic flexure and underwent a hemicolectomy and debulking without complications. She continued on gemcitabine and trastuzamab for six cycles with stable markers (CA125 range 50-210 kU/L). She progressed and failed three other traditional chemotherapy agents (capecitabine, liposomal doxorubicin, and etoposide) before ultimately succumbing to her disease. She died 50 months from time of diagnosis secondary to respiratory distress with massive intractable pleural effusions and pulmonary emboli.


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)

HER2 immunostaining and FISH of tumors from cases 1 and 2 (Case 2-sample from lung), who subsequently received trastuzumab either alone or in combination with conventional chemotherapy. Each tumor shows strong immunoreactivity for HER2 and amplification by FISH (HER2 probe -- red, CEP17 probe -- green).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: HER2 immunostaining and FISH of tumors from cases 1 and 2 (Case 2-sample from lung), who subsequently received trastuzumab either alone or in combination with conventional chemotherapy. Each tumor shows strong immunoreactivity for HER2 and amplification by FISH (HER2 probe -- red, CEP17 probe -- green).
Mentions: The first patient with recurrent mucinous carcinoma initially presented at age 19 with irregular periods, pelvic pain, increased abdominal girth, and an elevated CA125 of 110 kU/L (other markers normal). Imaging revealed a 15 cm mass and ascites. She underwent surgical staging including unilateral salpingoophorectomy (USO), appendectomy, omentectomy, peritoneal biopsies, and washings. Pathology reported a 20 × 15 × 14 cm mucinous BOT, intestinal type with focal inatraepithelial carcinoma of the ovary, all other specimens negative, stage Ia. She was observed and did well until 15 months later when she was noted to have an elevation in her CA125 to 81 kU/L. A CT scan revealed ascites and a mass in the contralateral ovary. She underwent USO and multiple biopsies. Pathology showed a mucinous borderline tumor of the ovary with intraepithelial carcinoma, but there were now implants of invasive mucinous carcinoma on the peritoneal surfaces. She received carboplatin and paclitaxel (CP) for six cycles, with normal CA125 throughout but again recurred four months after completion of therapy, based on reaccumulation of ascites, omental disease, elevated CA125 (130 kU/L), and abdominal symptoms. Pathology review of her first recurrence was performed to assess for molecular markers. This revealed the overexpression and amplification of HER2 (IHC 3+, HER2/CEP ratio 7.2) (Figure 3) and trastuzumab (6 mg/kg) was given in addition to single agent monthly carboplatin (600 mg/m2). A dramatic response, based on imaging and tumor markers, was noted after three cycles (Figure 4) and she completed a total of six cycles of this combination. She then received trastuzumab alone for three cycles with stable disease after which her markers began to rise and ascites and omental disease were seen on CT scan. Carboplatin was reintroduced but her markers continued to increase and she was changed to gemcitabine in combination with trastuzumab. Her CA125 level dropped from 1800 to 180 kU/L after the first cycle but she developed signs and symptoms of large bowel obstruction. She was taken to surgery for necrotic tumor in her cecum and splenic flexure and underwent a hemicolectomy and debulking without complications. She continued on gemcitabine and trastuzamab for six cycles with stable markers (CA125 range 50-210 kU/L). She progressed and failed three other traditional chemotherapy agents (capecitabine, liposomal doxorubicin, and etoposide) before ultimately succumbing to her disease. She died 50 months from time of diagnosis secondary to respiratory distress with massive intractable pleural effusions and pulmonary emboli.

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