In terms of prognosis, large cell neuroendocrine carcinoma is distinctly different from other non-small cell lung cancers. The prognosis of large cell neuroendocrine carcinoma was poor, even for early stage disease; the prognosis of the stage I disease of large cell neuroendocrine carcinoma was poorer than that of the same stage of other non-small cell lung cancers. Because of its aggressive clinical behavior and poor prognosis, large cell neuroendocrine carcinoma should be recognized as one of the poorest prognostic subgroups among primary lung cancers, and therefore novel therapeutic approaches should be established.

The World Health Organization histologic classification significantly correlated with the clinical stage. Tumor size, completeness of resection, histologic subtype, and stage predicted the prognosis of thymoma.

The pathologic features of invasion such as stromal disruption and pleural/vascular involvement have been shown to be of prognostic value in adenocarcinoma. However, the relationship between the degree of invasion, histologic subtype of adenocarcinoma, and prognosis remains unclear. We retrospectively studied 380 peripheral adenocarcinomas of < or = 2.0 cm in diameter with regard to histology and clinical profiles. Their degree of invasive growth was classified into four grades as follows according to the structural deformity and its location in the adenocarcinoma lesion: Grade 0 had a pure bronchioloalveolar growth pattern and no evidence of stromal invasion. Grade 1 had stromal invasion in the area of bronchioloalveolar growth. Grade 2 had stromal invasion localized on the periphery of a fibrotic focus. Grade 3 had stromal invasion into the center of a fibrotic focus. The clinicopathological data were obtained from medical records. The distribution of the histologic grade of invasion was as follows: grade 0 in 85 tumors (22%), grade 1 in 37 (10%), grade 2 in 46 (12%), and grade 3 in 212 (56%). This histologic grade of invasion was closely related to other indicators of tumor spread. Vascular/lymphatic permeation was seen in none of grade 0, in 1 lesion each of grade 1 and grade 2, and 144 (68%) of grade 3. Lymph node metastasis was seen in 57 (27%) lesions of grade 3 but not in grades 0, 1, or 2. The 5-year disease-free survival rates were 100%, 100%, 100%, and 59.6% for tumors with grade 0, grade 1, grade 2, and grade 3 invasion, respectively. Tumors with grade 1 and grade 2 invasion, like tumors with grade 0 invasion (bronchioloalveolar carcinoma), showed an excellent prognosis. Therefore, tumors with grade 1 and grade 2 invasion could be considered "minimally invasive" or "early" adenocarcinomas.

No abstract

Loss of heterozygosity on chromosome 22q has been detected in approximately 60% of advanced nonsmall cell lung carcinoma (NSCLC) as well as small cell lung carcinoma (SCLC), suggesting the presence of a tumor suppressor gene on 22q that is involved in lung cancer progression. Here, we isolated a myosin family gene, MYO18B, located at chromosome 22q12.1 and found that it is frequently deleted, mutated, and hypermethylated in lung cancers. Somatic MYO18B mutations were detected in 19% (14͞75) of lung cancer cell lines and 13% (6͞46) of primary lung cancers of both SCLC and NSCLC types. MYO18B expression was reduced in 88% (30͞34) of NSCLC and 47% (8͞17) of SCLC cell lines. Its expression was restored by treatment with 5-aza-2-deoxycytidine in 11 of 14 cell lines with reduced MYO18B expression, and the promoter CpG island of the MYO18B gene was methylated in 17% (8͞47) of lung cancer cell lines and 35% (14͞40) of primary lung cancers. Furthermore, restoration of MYO18B expression in lung carcinoma cells suppressed anchorage-independent growth. These results indicate that the MYO18B gene is a strong candidate for a novel tumor suppressor gene whose inactivation is involved in lung cancer progression.

The expression of c‐met/HGF receptor was evaluated in non‐small cell lung cancers (NSCLC) by western blot analysis of 11 established cell lines and 104 surgically resected tissues. All cancer cell lines (eight adenocarcinomas, two squamous cell carcinomas and a large cell carcinoma) showed strong c‐met protein bands of 145 kDa and 170 kDa. Moreover, c‐met protein was demonstrated in 34 (72.3%) of 47 surgically resected adenocarcinomas, 20 (38.5%) of 52 squamous cell carcinomas and 3 of 5 others, and the results were mostly confirmed immunohistochemically in formalin‐fixed and paraffin‐embedded tumors of the same case. Although squamous cell carcinomas showed relatively high c‐met protein expression in established cell lines, more adenocarcinomas than squamous cell carcinomas showed c‐met protein expression in the original cancers. Furthermore, two cell lines used in this study originated from primary cancers negative for c‐met protein expression, suggesting that c‐met protein expression might be influenced by cultivation. Furthermore, clinicopathological study revealed that NSCLC with c‐met protein expression tended to be in a higher pathological tumor stage and to have a worse outcome than those without such expression. In conclusion, c‐met protein is expressed in cell lines and primary tumors of NSCLC, and this phenomenon is probably closely related to the aggressive behavior or progression of NSCLC, especially of adenocarcinomas.

No abstract

To elucidate the contribution of beta-catenin gene mutation to the development of pulmonary blastomas, we analysed mutations in three well-differentiated fetal adenocarcinomas (WDFAs) and six biphasic pulmonary blastomas (BPBs). For comparison, eight clear-cell adenocarcinomas with fetal lung features were also examined. beta-Catenin gene mutations were found in all three WDFAs, two BPBs, and none of the clear-cell adenocarcinomas with fetal lung features. All tumours with mutations had a common histological feature, namely morule formation, and showed a characteristic heterogeneous beta-catenin expression pattern that was revealed by immunohistochemistry. Strong nuclear/cytoplasmic expression of beta-catenin was seen in clustered cells in the morular areas and in single cells in glands, and was associated with neuroendocrine differentiation. As beta-catenin mutations are rare among lung tumours, this distinctive genetic feature, which is also immunohistochemically detectable as overexpression with a heterogeneous pattern, has diagnostic significance. The presence of this common genetic alteration found in both WDFA and BPB implies a histogenetic linkage between these tumours.