Pulmonary Pleomorphic Carcinoma: A Clinicopathological Study Including EGFR Mutation Analysis

Kaira, Kyoichi; Horie, Yoshiki; Ayabe, Eriko; Murakami, Haruyasu; Takahashi, Toshiaki; Tsuya, Asuka; Nakamura, Yukiko; Naito, Tateaki; Endo, Masahiro; Kondo, Haruhiko; Nakajima, Takashi; Yamamoto, Nobuyuki

doi:10.1097/jto.0b013e3181ce3e3c

Cited by 109 publications

(98 citation statements)

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“…Thirty-three patients with advanced or recurrent non-adenocarcinoma NSCLC who had the somatic EGFR mutations and were treated with gefitinib were selected from 15 reports. (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) Table 1 summarizes the 15 identified clinical reports. The 15 reports included five prospective studies and 10 retrospective studies including four studies using the data of expanded access programs of gefitinib.…”

Section: Resultsmentioning

confidence: 99%

“…(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) The study included any reports based on the method of DNA isolation from fresh tissue or paraffin-embedded tissue, and the technique used to enhance tumor-derived DNA, which included either microdissection or use of the more sensitive polymerase chain reaction (PCR) amplification techniques. Not all consecutive NSCLC patients were included in the EGFR mutation analysis in every study.…”

Section: Methodsmentioning

confidence: 99%

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Efficacy of gefitinib for non‐adenocarcinoma non‐small‐cell lung cancer patients harboring epidermal growth factor receptor mutations: A pooled analysis of published reports

et al. 2011

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The efficacy of gefitinib for patients with non-adenocarcinoma non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is unclear, because only a small percentage of patients enrolled in the clinical trials to evaluate the efficacy of gefitinib for tumors harboring EGFR mutation were nonadenocarcinoma NSCLC. A pooled analysis was conducted to clarify the efficacy of gefitinib for non-adenocarcinoma NSCLC patients harboring EGFR mutations. A systematic search of the PUBMED databases was conducted to identify all clinical reports that contained advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations and treated with gefitinib. The selected patients were advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations who were treated with gefitinib and described in reports containing the data of the histology, status of EGFR mutations and response to gefitinib. This study selected 33 patients from 15 reports. Twenty-seven and three of the 33 patients were squamous cell carcinoma and adenosquamous cell carcinoma, respectively. One patient each had large-cell carcinoma, pleomorphic carcinoma and spindle cell carcinoma. Twenty-one patients (64%) had sensitive EGFR mutations. The response rate (RR), disease control rate (DCR) and median progression-free survival (mPFS) was 27%, 67-70% and 3.0 months, respectively. These factors were statistically significantly inferior in the non-adenocarcinoma NSCLC patients harboring EGFR mutations to adenocarcinoma patients harboring EGFR mutations selected from the same published reports (RR: 27% vs 66%, P = 0.000028; DCR: 67-70% vs 92-93%, P = 0.000014; mPFS: 3.0 vs 9.4 months, P = 0.0001, respectively). Gefitinib is less effective in non-adenocarcinoma NSCLC harboring EGFR mutations than adenocarcinoma harboring EGFR mutations. (Cancer Sci 2011; 102: 1032-1037 G efitinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), is used for the treatment of non-small-cell lung cancer (NSCLC). Two study groups have demonstrated the presence of EGFR mutations in some NSCLC patients and reported higher response rates (RR) to gefitinib therapy among these patients.(1,2) The deletion of exon 19 and point-mutation of exon 21 from T to G at codon 858 (L858R) are the most frequently encountered EGFR mutations, accounting for 90% of all the cases.(3) Approximately 3% of the mutations occur at codon 719 resulting in the substitution of glycine to cysteine, alanine or serine (G719X). In addition, approximately 3% are in-frame insertion mutations in exon 20.(4) The RR was the highest in patients with exon 19 deletions followed by L858R and G719X (81%, 71% and 56%, respectively).(5) In contrast, there are no reports of a single patient with the exon 20 insertion mutation who responded to EGFR-TKI.(5) Clinical trials were conducted based on these findings, which showed that gefitinib is an effective treatment option for first-line treatment in NSCLC patients harboring sensitive EGFR mutations with median progressio...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Efficacy of gefitinib for non‐adenocarcinoma non‐small‐cell lung cancer patients harboring epidermal growth factor receptor mutations: A pooled analysis of published reports

et al. 2011

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“…PPC is defined as a poorly differentiated non‐small cell lung cancer (NSCLC) containing spindle cells and/or giant cells, or a carcinoma that comprises spindle or giant cells alone, in at least 10% of the tumor 4. It has an aggressive clinical course and can show resistance to chemotherapy, which is an actively applied treatment for NSCLC 5, 6. The present case of PPC was unresponsive to EGFR‐TKIs despite harboring an EGFR mutation.…”

Section: Discussionmentioning

confidence: 88%

“…Several researchers have reported that the frequency of PPC harboring EGFR mutations is approximately 15% 6, 7, 8, 9. However, it is still unclear whether EGFR‐TKIs are active against this type of PPC.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary pleomorphic carcinoma: A case harboring EGFR mutation treated with EGFR‐TKIs

et al. 2018

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Pulmonary pleomorphic carcinoma (PPC) is a very rare type of primary lung cancer with an aggressive clinical course. Few reports have documented therapeutic options for PPC with EGFR mutations. Herein, we report a case of PPC with EGFR mutation treated with EGFR‐tyrosine kinase inhibitors (TKIs). A 65‐year‐old Japanese woman was diagnosed with stage IV lung adenocarcinoma with L858R point mutation in exon 21. Despite treatment with erlotinib, the patient died after two weeks as a result of rapid disease progression. Postmortem examination indicated that the thoracic tumors consisted primarily of spindle/sarcomatous components, while expression of the mutated EGFR protein was only observed in adenocarcinoma components. We speculate that the tumor was not driven by EGFR mutation. Clinicians should bear in mind the possibility of pleomorphic carcinoma if EGFR‐TKI treatment fails to achieve a clinical response for adenocarcinoma harboring an activating EGFR mutation diagnosed on the basis of small biopsy specimens.

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“…Since the vascular invasion was associated with a poor prognosis, there is a possibility that vascular endothelial growth factor (VEGF) inhibitor would be effective for PC patients. Regarding the genetic profile of PC, some cases of EGFR activating mutation have been reported (13). Kobayashi et al reported the case of transformation to sarcomatoid carcinoma in ALK-rearranged adenocarcinoma (18).…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological factors influenced the prognosis of surgically resected pulmonary pleomorphic carcinoma

et al. 2017

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Background: Pulmonary pleomorphic carcinoma has made an unfavorable prognosis because of its properties of resisting radiation and chemotherapy, and its aggressive growth. The correlation between clinicopathological factors and prognosis about pulmonary pleomorphic carcinoma patients who received its surgical resection has not been clearly identified. Methods:We retrospectively investigated the clinical records of 24 pulmonary pleomorphic carcinoma patients who had a surgical resection from January 2004 to December 2013 at our institute. We examined the correlation between their clinicopathological factors and therapeutic effects including their prognosis.Results: The median follow up time was 2.3 years. The 5-year survival was 54.7% and the 5-year progression free survival was 52.4%. In comparison with other tissue types of lung cancer, the prognosis was not so poor even taking into consideration the survival curve including several progression stages. We analyzed the 21 clinicopathological factors in order to clarify the factors connected with the prognosis and disease progression. As a result, we found that both vascular invasion evaluated by immunohistochemistry and lymph node metastasis were connected closely with the overall survival. We found another strong link between the tissue type of epithelial components, vascular invasion evaluated by immunohistochemistry and lymph nodal metastasis with the progression free survival. Conclusions:Pulmonary pleomorphic carcinoma patients with lymph node metastasis and vascular invasion had worse prognosis after their surgical resections. We have to find an effective chemotherapeutic drug or molecular targeted drug.

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Pulmonary Pleomorphic Carcinoma: A Clinicopathological Study Including EGFR Mutation Analysis

Abstract: EGFR mutation was recognized in approximately 20% of patients with pulmonary pleomorphic carcinoma. It is necessary to investigate whether the use of a molecular targeting drug improves outcome for pulmonary pleomorphic carcinoma.

Cited by 109 publications

References 20 publications

Efficacy of gefitinib for non‐adenocarcinoma non‐small‐cell lung cancer patients harboring epidermal growth factor receptor mutations: A pooled analysis of published reports

Efficacy of gefitinib for non‐adenocarcinoma non‐small‐cell lung cancer patients harboring epidermal growth factor receptor mutations: A pooled analysis of published reports

Pulmonary pleomorphic carcinoma: A case harboring EGFR mutation treated with EGFR‐TKIs

Clinicopathological factors influenced the prognosis of surgically resected pulmonary pleomorphic carcinoma

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