Subset Of Small Cell Lung Cancer Research Articles

Sequential occurrence of non-small cell and small cell lung cancer with the same EGFR mutation

We report a case of small cell lung cancer (SCLC) developing after prolonged treatment (more than 2 years) for primary adenocarcinoma of the lung, and we show that both the SCLC and non-small cell lung cancer (NSCLC) tissues obtained from the same site share the same deletion in exon 19 of EGFR. This case suggests that the activating EGFR mutations may confer the pathogenesis of a subset of SCLC.

Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer.

Embryonic signalling pathways regulate progenitor cell fates in mammalian epithelial development and cancer. Prompted by the requirement for sonic hedgehog (Shh) signalling in lung development, we investigated a role for this pathway in regeneration and carcinogenesis of airway epithelium. Here we demonstrate extensive activation of the hedgehog (Hh) pathway within the airway epithelium during repair of acute airway injury. This mode of Hh signalling is characterized by the elaboration and reception of the Shh signal within the epithelial compartment, and immediately precedes neuroendocrine differentiation. We reveal a similar pattern of Hh signalling in airway development during normal differentiation of pulmonary neuroendocrine precursor cells, and in a subset of small-cell lung cancer (SCLC), a highly aggressive and frequently lethal human tumour with primitive neuroendocrine features. These tumours maintain their malignant phenotype in vitro and in vivo through ligand-dependent Hh pathway activation. We propose that some types of SCLC might recapitulate a critical, Hh-regulated event in airway epithelial differentiation. This requirement for Hh pathway activation identifies a common lethal malignancy that may respond to pharmacological blockade of the Hh signalling pathway.

Absence of p16(INK4) protein is restricted to the subset of lung cancer lines that retains wildtype RB: Otterson GA, Kratzke RA, Coxon A, Kim YW, Kaye FJ. NCI-Navy Oncology Branch, Naval Hospital, Bethesda, MD 20889. Oncogene 1994; 9: 3375–3378

Cell cycle dependent phosphorylation of the RB tumor suppressor protein is mediated by a family of G1 cyclin dependent kinases (cdks) and cyclins including the activated cdk4:cyclin D complex. The identification of a cdk4 inhibitor, p16INK4, as a target for mutations in cultured tumor lines and primary tumors suggested that RB activity may be affected in these cells. We have examined 88 lung cancer lines for p16INK4 protein expression and have observed a striking inverse correlation between the presence of p16INK4 and wildtype RB. We demonstrated that only 6/55 (11%) of small cell lung cancer (SCLC) samples had absent p16INK4 protein, and all 6 belonged to the rare subset of SCLC with wildtype RB expression. Conversely of 48 SCLC samples with absent or mutant RB, all showed detectable levels of p16INK4 protein. In contrast, we observed that 23/33 (70%) of non-SCLC samples had loss of p16INK4. Twenty-two of 26 non-SCLC lines with wildtype RB had absent p16INK4 while 6 of 7 non-SCLC lines with absent or mutant RB had detectable p16INK4. The inverse correlation of RB and p16INK4 expression and the absence of p16INK4 inactivation in RB (-/-) SCLC lines (0/48) confirms a common p16INK4/RB growth suppressor pathway in human cancers and provides evidence that p16INK4, and not an adjacent gene on chromosome 9p, is a specific target for mutational events.

Pretreatment natural history of small cell lung cancer presenting as a solitary pulmonary nodule: Urschel JD. Div. Thoracic Surgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263-0001. J Carciovasc Surg 1994;35:273–275

Small cell lung cancer (SCLC) occasionally presents as an asymptomatic solitary pulmonary nodule (SPN) on chest radiography. This group of SCLC patients appears to have different tumor growth properties and greater potential for cure than most SCLC patients. Some investigators have hypothesized that SCLC presenting as a SPN represents a biologically unique subset of SCLC.To provide support for this hypothesis, uncontrolled but infrequently obtainable natural history observations are reported.A retrospective radiograph review of selected patients with SCLC presenting as a SPN was done.Teaching hospital.Three patients with delay in treatment of SCLC were reviewed.Slow growth of SPNs was documented over a 14, 27, and 40 month period in these patients. No lymph node or systemic metastases were found. Radiographic observations were made retrospectively; delayed treatment of the SPNs was not intentional. SCLC was diagnosed by pulmonary resection in two patients and fine needle aspiration cytology in one patient.The hypothesis that SCLC presenting as a SPN is a biologically unique subset of SCLC, with relatively slow growth and potential for cure, is supported by these uncontrolled observations.

The Release of Chromogranin A and B Like Activity from Human Lung Cancer Cell Lines: A Potential Marker for a Subset of Small Cell Lung Cancer

Human small cell lung cancer (SCLC) is in vivo and in vitro characterized by a heterogeneous spectrum of neuroendocrine markers. The non-SCLC group is deprived of these markers, or expresses them in low quantities. In this paper we report on the release to the culture medium of neuroendocrine associated proteins, chromogranin A and B like activity (CABLA). The culture medium from three out of five SCLC cell lines and in one/five non-SCLC cell line contained significant levels of CABLA. Normal diploid foreskin fibroblasts and a histiocytic lymphoma cell line were deprived of CABLA production. The presence of CABLA in both SCLC and non-SCLC further stress their common histogenetic origin. The CABLA values were partly unrelated to other neuroendocrine markers. Determinations of CABLA could thus be a potential and valuable marker for a subset of SCLC.

Amplification, expression and rearrangement of c-myc and N-myc oncogenes in human lung cancer.

Human lung cancers can be divided into two major classes according to their clinical, histological, biochemical, and karyotypic properties: non-small cell lung cancer (NSCLC) (adenocarcinoma, epidermoid, large cell carcinoma) and “oat cell” or small cell lung cancer (SCLC) (Minna 1982; Gazdar 1980; Baylin 1980; Gazdar 1981a; Whang Peng 1982a). Of particular interest is a subset of SCLC, the morphological and biochemical variants (SCLC-V) (Gazdar 1981a; Radice 1982; Carney 1983). These variants can be seen histologically in approximately 6-15% of diagnostic biopsy specimens before any chemo- or radiotherapy treatment is given (Radice 1982; Hirsch 1983). At autopsy, approximately 30–40% of patients previously thought to have “pure” SCLC histologically will have these variant cells. Finally, patients with variant cells in their diagnostic biopsies have a fulminant course with inferior response to chemo- and radiotherapy and a much shorter survival than patients with “pure” SCLC (Radice 1982). Thus, clinically this SCLC-V group is quite significant.KeywordsSmall Cell Lung CancerHuman Small Cell Lung CancerOncogene AmplificationSmall Cell Lung Cancer TumorSmall Cell Lung Cancer LineThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.