Purpose: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC.Experimental Design: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis.Results: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCCspecific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non -small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC.Conclusion: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.

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Background: Pleomorphic carcinoma of the lung is a malignant epithelial tumor that contains carcinomatous and sarcomatoid components. Due to its rarity, few studies have been reported, and its clinical and pathological characteristics remain unclear.Method: We retrospectively investigated 22 cases of pleomorphic carcinoma of the lung.Results: Fifteen cases were diagnosed by surgical resection, four by autopsy, and three by transbronchial biopsy. Nineteen patients were male and three were female, and their mean age at diagnosis was 68.3 years (± 10.1).Eighteen were current-or ex-smokers with substantial smoking histories (mean 46.4 pack-years). Sixteen patients had symptoms: hemoptysis and cough were commonly seen. Chest computed tomography (CT) findings revealed that the tumors were quite large (mean diameter 45.3 ± 21.9 mm; range 14-110 mm), and 21 tumors were peripherally located. Positron emission tomography with 18-fluorodeoxy-glucose (FDG-PET) was performed in 12 patients, and the Standardized Uptake Value (SUV) tended to be high (9.44 ± 4.98). In the 15 patients who underwent surgical resection, recurrence was common; systemic metastases were also frequently found. Patients who had received surgical 3 treatment with proper follow-up care survived longer than those who did not undergo surgery. Responses to chemotherapy were generally poor, although one patient exhibited partial response to gefitinib.Conclusions: Pulmonary pleomorphic carcinoma has strong malignant potential with frequent distant metastases, as has already been reported. However, this study demonstrated that surgical treatment and appropriate follow-up therapy might result in better prognoses.

BACKGROUNDOccasionally, medically compromised and/or elderly patients with nonsmall cell lung carcinomas (NSCLCs) cannot be treated surgically. We investigated small‐volume hypofractionated image‐guided radiotherapy (IGRT) without the need for breath control in patients with inoperable Stage I NSCLCs.METHODSBetween September 1996 and September 1999, 22 patients with Stage I NSCLCs, including 19 males and 3 females, were treated with IGRT. Among these patients, there were 13 Stage IA and 9 Stage IB tumors. The tumors ranged in size from 14.2 to 58.5 mm, with a median size of 26.7 mm. Of the 22 patients, 19 were unfit for surgical treatment due to poor pulmonary function, complications, and/or advanced age and 3 refused surgery. Computed tomographic scans (CT) of the primary tumor were taken during three respiratory phases and they were analyzed to determine the planning target volume, which included only the primary tumor with allowances for respiratory movement. The radiation doses administered at the edge of the moving tumor during normal breathing were 80% of the prescribed dose, either 48 or 60 Gy given in eight fractions over 2 weeks. Clinical evaluation, chest CT scan, and pulmonary function tests were performed before irradiation and at regular intervals for the post‐IGRT follow‐up. The median follow‐up period was 24 months (range, 2–44 months; mean, 21.8 months) (at least 24 months for survivors).RESULTSOf 17 tumors assessed at the initial follow‐up 2–6 months after treatment (5 complete responses, 11 partial responses, and 1 progressive disease), 16 (94%) were controlled locally. One local recurrence was observed during the follow‐up. The lung carcinoma‐specific survival rate at 1 year was 94% and the 1‐year actuarial recurrence‐free survival rate was 71%. The lung carcinoma‐specific survival rate at 2 years was 73% and the 2‐year actuarial recurrence‐free survival rate was 67%. The treatment was well tolerated and no major side effects were observed. Localized radiation pneumonitis was observed in all patients who were examined by CT scan, but the patients were asymptomatic. Parameters of pulmonary function, including vital capacity, total lung capacity, and diffusion capacity for carbon monoxide, decreased very little or not at all, indicating that IGRT rarely deteriorated pulmonary functions.CONCLUSIONSSmall‐volume hypofractionated IGRT without breath control is a feasible and beneficial method for the curative treatment of patients with Stage I NSCLCs. It has the potential of a high local tumor control rate and low morbidity. Cancer 2002;95:1546–53. © 2002 American Cancer Society.DOI 10.1002/cncr.10853