Small Cell Anaplastic Carcinoma Research Articles

Epidermal growth factor receptor variants in patients from Myanmar with lung adenocarcinoma

Abstract Background Epidermal growth factor receptor (EGFR) sequence variants in patients from Myanmar have not yet been reported. Objectives To describe the molecular epidemiology of EGFR variants in patients from Myanmar with lung adenocarcinoma. Methods Histological diagnosis and categorization of biopsies collected from 66 patients (28–78 years) with lung cancer was conducted using a panel of antibodies including those to: TTF1, P40, synaptophysin, CK7, and napsin-A. Samples from patients with confirmed adenocarcinoma were tested for EGFR variants using a cobas EGFR Mutation Test kit and cobas z 480 System (Roche). We conducted a univariate analysis of categorical factors using a χ2 or Fisher exact test. Results Histological types were adenocarcinoma (61%, 40/66), squamous cell carcinoma (24%, 16/66), neuroendocrine carcinoma (9%, 6/66), undifferentiated carcinoma (2%, 1/66), adenosquamous carcinoma (2%, 1/66), small cell anaplastic carcinoma (2%, 1/66), and pleomorphic sarcoma (2%, 1/66). EGFR variants were detected in 15 of 40 (38%) cases of adenocarcinoma. Among them, 6 patients (40%) had an exon 19 deletion, another 6 (40%) had exon 21 substitutions, 1 (7%) had exon 20 insertion S768I, and 2 (13%) had compound variations (1 of exon 21 L858R and exon 18 G719X, and 1 of exon 20 S768I and exon 18 G719X). Although limited by small sample size, no significant association was found between the variants and factors including family cancer history, age group, sex, ethnicity, or occupation. However, there was a strong significant association between never-smokers and EGFR variants (P = 0.008). Conclusion Knowledge of EGFR variants in patients from Myanmar is encouraging for their effective cancer treatment.

The role of prophylactic radiotherapy in prevention of brain metastasis

Despite of these side effects, many studies concluded that the benefits of prophylactic brain radiation in prevention and delaying the spread of cancer overcome its harmful effects. This review aimed to evaluate the literature assessing the role of prophylactic radiotherapy in prevention of metastasis to the brain tissues, measure its incidence and the overall survival rates in patient with lung cancer to provide evidence-based data Methods: Electronic search was performed in Medline using Pubmed resulted in 107 eligible studies. The titles and abstracts of all these articles, was screened and based on this reading studies excluded due to irrelevancy or duplication. Results: Search of the literature identified total of 107 studies, after exclusion of irrelevant, duplicated and review studies, five studies were included in the review as they met the inclusion criteria. The included studies pointed to assess the effect of prophylactic radiotherapy in avoidance of brain metastasis. All included studies were randomized controlled trials. Total numbers of 1399 patients were recruited in the included studies. Age of patients range from 39 up to 84 years old or more. Small-cell lung cancer was the primary cancer in three of the included studies. One of the included studies assessed patients with non-small cell lung cancer and one study included patients with small cell anaplastic bronchogenic carcinoma. Conclusions: The use of prophylactic radiotherapy is effective in reduction of incidence of brain metastasis, but it had no role in rising of the overall survival.

The role of prophylactic radiotherapy in prevention of brain metastasis

Despite of these side effects, many studies concluded that the benefits of prophylactic brain radiation in prevention and delaying the spread of cancer overcome its harmful effects. This review aimed to evaluate the literature assessing the role of prophylactic radiotherapy in prevention of metastasis to the brain tissues, measure its incidence and the overall survival rates in patient with lung cancer to provide evidence-based data Methods: Electronic search was performed in Medline using Pubmed resulted in 107 eligible studies. The titles and abstracts of all these articles, was screened and based on this reading studies excluded due to irrelevancy or duplication. Results: Search of the literature identified total of 107 studies, after exclusion of irrelevant, duplicated and review studies, five studies were included in the review as they met the inclusion criteria. The included studies pointed to assess the effect of prophylactic radiotherapy in avoidance of brain metastasis. All included studies were randomized controlled trials. Total numbers of 1399 patients were recruited in the included studies. Age of patients range from 39 up to 84 years old or more. Small-cell lung cancer was the primary cancer in three of the included studies. One of the included studies assessed patients with non-small cell lung cancer and one study included patients with small cell anaplastic bronchogenic carcinoma. Conclusions: The use of prophylactic radiotherapy is effective in reduction of incidence of brain metastasis, but it had no role in rising of the overall survival.

Épithéliomas bronchiques à petites cellules et métastases cérébrales de leur traitement à leur prévention

Brain metastasis is a common feature of small cell anaplastic lung carcinoma and their treatment represent a challenge due to the neurological complication. The different forms of treatment will be reviewed as well as the prevention of brain metastases by a prophylactic brain irradiation.

Neuroendocrine small cell rectal cancer metastasizing to the liver: a unique treatment strategy, case report, and review of the literature

We describe the treatment of a 46-year-old Saudi man with advanced stage liver metastatic neuroendocrine rectal cancer. The patient presented with a large liver lesion and rectal bleeding. He was cachectic, with a firm tender mass 20 mm above the anal verge. Computed tomography (CT) showed a mass 9.5 × 13 cm in size in the right hemi-liver, abutting the middle hepatic vein. The patient refused treatment, and consulted another hospital. After 3 months, he presented with the same symptoms in addition to delirium. Colonoscopy showed an ulcerating anorectal mass, from which a biopsy was taken. Repeat CT showed an increase in the size of the liver lesion to 17 cm and no change in the pelvis. The final histopathology report identified anaplastic small cell carcinoma. The patient underwent extended right liver resection followed by abdominoperineal resection, then 13 cycles of chemotherapy and monthly somatostatin injections. At the most recent follow-up, the patient had been disease-free for 48 months. Surgical resection (R0) of the primary and secondary tumor, followed by platinum-based chemotherapy can result in good survival in cases of small cell carcinoma with large liver metastasis, irrespective of whether the primary or secondary tumor is resected first.

Rheumatoid nodule and combined pulmonary carcinoma: topographic correlations; a case report and review of the literature.

An association between rheumatoid arthritis (RA) and malignancies has been ascertained and patients with RA appear to be at higher risk of lymphoma and lung cancer. The higher risk of the latter malignancy may be related to rheumatoid interstitial lung disease and immunosuppressive therapies. Herein we illustrate the case of a 59-year-old male smoker affected by RA and treated with cortisone, methotrexate and TNF-α antagonists, who underwent right lower lobectomy for a nodular lesion. On microscopic examination, the lesion consisted of two distinct areas: a central area of fibrinoid necrosis, bordered by histiocytes in a palisaded arrangement, lymphocytes and a 0.4 cm thick peripheral area constituted by a combined small cell anaplastic carcinoma, adenocarcinoma and squamous cell carcinoma. The combination of three histotypes is very rare in such a small tumour. In our case, it may be hypothesized that synchronous, heterogeneous mutations occurred in different type of committed cells or in stem cells, due to the production of cytokines by RA nodule histiocytes and lymphocytes, which are contiguous to the carcinomatous area. Since few studies have evaluated the topographic correlation between tumors and rheumatoid lung lesions, further morphological and molecular studies are needed to clarify this association and the pathogenetic relationship between RA and cancer of the lung.

Cisplatin as a cornerstone of modern chemotherapy

35 years have passed since Higby and colleagues demonstrated the clinical activity of cisplatin in a broad spectrum of tumours. Although platinum derivatives are now familiar in medical oncology, this group’s land mark study, published in 1974, had a major eff ect on chemotherapy combinations over subsequent years. In 1965, Rosenberg and co-workers found that the discharge of an electric current from a platinum electrode inhibited the replication of Escherichia coli, before going on to isolate several platinum-containing compounds from the culture medium that were found to cause nucleic-acid alkylation. 4 years later, platinum derivatives were recognised as a new class of anti-cancer drugs with promising pre-clinical activity. Higby and colleagues investigated the activity of cisdiaminodichloroplatinum (DDP, cisplatin) in a phase I study. The trial was divided into two parts, although neither the exact number of patients treated nor the exact inclusion and exclusion criteria are explicitly mentioned in the paper. In the fi rst part of the study, cisplatin was infused intravenously over 3–5 min according to two diff erent schedules (50–100 mg/m2 as a single dose or 18–24 mg/m2 daily for 5 days). Irreversible renal toxicity occurred in fi ve of nine patients receiving cisplatin as a single dose and in two of fi ve patients treated with a daily dose for 5 days. Severe nausea and emesis occurred in almost all patients, and high-frequency hearing loss was noted in fi ve patients. Haematological toxicity was mild. Two patients with persistent increases in serum creatinine died; both patients had received gentamicin despite renal dysfunction. Pathological examination of kidney biopsy samples from both patients showed acute tubular necrosis lesions. In the second part of the study, patients received cisplatin 20 mg/m2 daily for 5 days. Of 11 patients with testicular tumours refractory to conventional therapy (doxorubicin and dactinomycin at this time), two complete and four partial responses were observed. Long-lasting responses were also seen in patients with anaplastic small-cell carcinoma of the thyroid and transitional-cell carcinoma of the bladder (one each). Hence, Higby and colleagues reported high response rates (close to 50%) in patients with testicular cancer, irrespective of histological subtype. By contrast, response rates in phase I oncology trials done between 1991 and 2002 were close to 10%, although death rates in modern phase I trials average 0·5%, probably lower than that reported by Higby and colleagues. In addition to effi cacy data, this study provided important information on cisplatin’s toxicity: a high emeto genic potential, acute and cumulative nephrotoxicity, and a risk of high-frequency hearing impairment. Peripheral neuropathy, another important toxicity of cisplatin, was later reported in patients receiving higher cumulative doses of the drug. Renal toxicity was subsequently shown to be reduced by osmotic diuresis and forced hydration. On the basis of this study, cisplatin became part of chemotherapy regimens that still constitute the gold standard for treatment of sarcomas and cancers of the testes, ovaries, bladder, head and neck, and lungs. During the 1980s and 1990s, other platinum derivatives devoid of renal toxicity—carboplatin and oxaliplatin—were developed, broadening the spectrum of activity of platinum derivatives, and establishing these drugs as a cornerstone of modern chemotherapy.

Metastasen-induzierte akute Pankreatitis beim Bronchialkarzinom

Pancreatic metastases were found in 14 of 250 patients (5.6%) with bronchial carcinoma. The most common histological type leading to pancreatic metastases was the small-cell anaplastic carcinoma (86%). Metastasis-induced pancreatitis is rare, having been noted in only one patient (metastases in the head of the pancreas). In two other patients acute pancreatitis was found by autopsy which, however, had been clinically silent. In the other eleven the pancreatic metastases were also clinically silent.

Numb cheek syndrome as the first manifestation of anti–Hu paraneoplastic neuronopathy

Sirs: Unilateral numb cheek syndrome (NCS) has rarely been described as the first manifestation of malignancy due to neoplastic involvement of the trigeminal nerve, more specifically the maxillary branch [1, 2]. NCS as the first symptom of subacute paraneoplastic sensory neuronopathy has, to the best of our knowledge, never been reported. We present this case because its rarity led to a diagnostic delay of several months. A 47-year-old man presented with a one month history of numbness in the left cheek, both inner and outer surfaces. The area of numbness corresponded with the mandibular division of the left trigeminal nerve (V3). His medical history was unremarkable. Neurological examination was normal including the left V3 area. As the main part of the cheek is innervated by the buccal nerve we considered that our patient had a mandibular sensory neuropathy probably due to compression or infiltration of the nerve by local malignancy, as seen in other types of trigeminal mononeuropathy [3]. Ancillary investigations including contrast enhanced brain MRI, thorax CT and extensive laboratory examinations of the blood and urine were normal. Cerebrospinal fluid (CSF) examination revealed mild lymphocytic pleocytosis, slightly elevated protein of 0.69 g/l (0.2–0.5) and no malignant cells or oligoclonal bands. Although intracranial malignancy could not be ruled out an expectant policy was chosen by the patient. Two months later he complained of slightly unsteady gait. A second MRI of the brain and skull base was normal. Another 4 months later he noticed numbness of his left hand and foot. Neurological examination showed only left sided facial hypalgesia. Nerve conduction studies were consistent with a non uniformly distributed, predominantly axonal, sensorimotor neuropathy, most pronounced in the left extremities. Repeated conventional CSF examination only showed an increased protein level of 0.86 g/l. Anti-Hu antibodies in CSF were detected with indirect immunofluorescence and Western blotting techniques. A second thorax CT and whole body PET-scan eventually showed a solitary lesion in the right hilus, which proved to be a metastasis of an anaplastic small cell carcinoma on histological examination. Although the primary tumour remained unrevealed, a paraneoplastic multifocal mainly sensory neuronopathy associated with presumed primary small cell lung carcinoma was diagnosed and combined chemotherapy started. Fifteen months after the initial complaint the primary tumour remained undetected and no metastases were found. The neuropathy progressed resulting in very severe sensorimotor neuropathy with asymmetric painful paresthesias, diffuse proprioceptive loss and weakness in all extremities. In patients with paraneoplastic anti-Hu associated neuropathy (AHN) involvement of the cranial nerves may be present but is very rarely the presenting symptom. AHN most commonly presents as a subacute sensory neuropathy, less frequently as a sensorimotor neuropathy [5, 6]. These neurological symptoms typically antedate the diagnosis of cancer and most commonly involve the extremities [4–7]. In 306 patients with malignancy and associated anti-Hu antibodies, 50 % of the patients had a sensory neuropathy [4–6]. Three of them had trigeminal nerve involvement, but in no one was cheek numbness described as the only presenting symptom. As initially no primary tumour was found, we did not consider AHN as a potential cause of the unilateral cheek numbness in our patient. The final diagnosis was reached because of the extension of the sensory symptoms and eventually the evidence of an asymmetric sensorimotor neuropathy. The diagnostic delay between the NCS and final diagnosis was 6 months, which lies within the range of reported diagnostic delays in AHN patients [4–7]. As early treatment of the underlying malignancy is the mainstay of treatment, we report this patient in order to add NCS to the list of presenting symptoms of AHN.

脾臓転移を認めた腎小細胞癌の一例

A 67-year-old male visited a hospital with a complaint of right flank pain. A computed tomography and magnetic resonance imaging demonstrated a right renal tumor, lymphadenopathy, and a splenic tumor. Right radical nephrectomy, lymph node dissection, and splenectomy were performed. Histological examination of the renal tumor and lymph node revealed small cell anaplastic carcinoma. A dilated renal pelvis was focally covered with transitional cell carcinoma grade 2. Splenic tumor revealed a mixture of small cell and giant cell anaplastic carcinoma. Immunostaining for NSE and cytokeratin were positive. He received 2 courses of adjuvant chemotherapy with cisplatin and etoposide. The patient is alive for 10 months after surgery and free of carcinoma. This is the 10th case of renal small cell carcinoma reported in Japan. The clinical features and managements of these rare tumors are discussed.

Gastrin releasing peptide and gastrin releasing peptide receptor expression in gastrointestinal carcinoid tumours

Aims: To establish whether gastrin releasing peptide (GRP) and the GRP receptor (GRPR) are expressed together in gastrointestinal carcinoid tumours. Methods: Twenty six carcinoid tumours from the stomach, small intestine,...

The mutator phenotype theory of carcinogenesis and the complex histopathology of tumours: support for the theory from the independent occurrence of nuclear abnormality, loss of specialisation and invasiveness among occasional neoplastic lesions.

The mutator phenotype theory of carcinogenesis suggests that genetic instability is an early and essential part of tumour development. This instability provides for substantially random cell-to-cell genomic variation (genomic heterogeneity) to arise among cells of individual tumours. Genetically unstable cells then produce 'successful' clones of cells with the necessary mutations for malignant behaviour. In a previous paper (Bignold L. P., Cell. Mol. Life Sci. 2002; 59: 950-958), it was pointed out that a population of cells which is heterogeneous for behaviour-related genes may well also be heterogeneous for morphology-related genes. This would result in cellular pleomorphism among cells of individual tumours, and so explain this almost universal characteristic of solid malignancies. paragraph sign If the concept of random genomic variability applies fully to the histopathology of tumours, then most tumours should show a mixture of neoplastic features, especially nuclear atypia, loss of specialised function (such as loss of production of mucus by glandular cells) and invasiveness. However, occasional lesions might be expected to occur which show these characteristics independently. That is, lesions should exist which exhibit one or two of the three characteristics of neoplasms without the other(s). paragraph sign This paper identifies, among human tumours, lesions which show independence of these characteristics. Two of the examples discussed are a Bowenoid solar keratosis that shows severe nuclear atypia, but no apparent loss of specialisation and no invasiveness. On the other hand, anaplastic small cell carcinoma of the lung often exhibits marked loss of differentiation, very aggressive invasion and metastasis, but little nuclear pleomorphism. paragraph sign These examples are considered to provide further support for the importance of the mutator phenotype to the pathogenesis of neoplasia.

The usefulness of a panel of immunostains in the diagnosis and differentiation of metastatic malignancies in pericardial effusions

Pericardial effusions are not uncommon in patients with an advanced malignancy Rarely malignancies may present initially with a pericardial effusion. Cytological examination of pericardial fluid may be valuable in differentiation of these cases. However, a metastatic tumour in serous effusion may not always show the functional differentiation of the primary tumour. In such a situation, although a wide range of special studies have been suggested for the diagnosis of malignancy we have found the use of a panel of a few common immunostains to be useful in confirming or suggesting the site of a primary tumour. The material for this study consisted of 76 pericardial fluids obtained between January 1991 and October 1998 from 46 males (mean age 59 years) and 30 females (mean age 52 years). Metastatic malignancy was diagnosed in 22 of the 76 patients and in 7/22 cases pericardial effusions were the initial presentation. The subsequent follow-up in the seven cases revealed adenocarcinoma of lung (n = 2), small cell anaplastic carcinoma of lung (n = 1), squamous cell carcinoma lung (n = 1), melanoma leg (n = 1), non-Hodgkin's lymphoma retroperitoneal lymph nodes (n = 1) and carcinoma of the breast (n = 1). Of the remaining 15 cases with a known history of malignancy, eight had cancers (three adeno; two small cell; one poorly differentiated, and two squamous cell types) of the lung; breast (n = 3); colon (n = 1); melanoma (n = 2) and non Hodgkin's lymphoma (n = 1). Immunostains which were useful in the diagnosis were EMA, CEA, cytokeratin, B72.3, HMB45, vimentin, S100, LCA, L26 and kappa and lambda light chains.

Aspiration cytodiagnosis of small cell malignancies found in fine needle aspirate (FNA) of the liver: an immunocytochemical study

In this study the features of small cell malignancies found in the liver by fine needle aspiration cytology (FNAC) and immunostains required for a diagnosis and differential diagnosis are presented. The material consisted of 197 fine needle aspirates which were performed under image guidance between January 1982 to October 1999. Of these, 30 were diagnosed as small cell malignancies. The age of patients ranged between 46 and 68 years. The aspirated material was examined using Papanicolaou-stained filter preparations and cell blocks, the latter stained with hematoxylin and eosin and a panel of immunoperoxidase stains. The diagnoses based on a correlation of relevant clinical history, cytohistological findings and immunostaining were: metastatic small cell anaplastic carcinoma of lung (n = 6); neuroendocrine tumour (n = 9); non-Hodgkin's lymphoma (n = 4); well-differentiated cholangiocarcinoma (n = 2); metastatic carcinoma of the prostate (n = 2); metastatic adenocarcinoma (n = 4) and metastatic carcinoma breast (n = 3). This study emphasizes the wide range of neoplasms that enter into the differential diagnosis of small cell malignancies found in the liver and a correlation of clinical, cytohistological and immunostaining findings which seem to be useful in suggesting a diagnosis.

Do morphology and stage explain the inferior lung cancer survival in Denmark?

Danish lung cancer patients diagnosed during 1983-1987 experienced 5-yr relative survival rates 2-7% inferior to patients in the other Nordic countries, despite the similarity of cancer registration and healthcare systems in the Nordic countries. Is the inferior relative survival in Denmark due to differences in morphology or stage of lung cancers? The present study compared in detail the survival of 92,719 patients diagnosed with lung cancer during 1978-1992 in Denmark, Finland, and Norway. In particular, differences in morphology and extent of disease were studied. A poor survival rate for small cell anaplastic lung carcinoma compared with all other morphologies was confirmed. However, this could not explain the relative survival differences observed between countries. Extent of disease was the most important predictor of survival. Part of the observed survival differences could be explained by a less favourable stage distribution in Denmark, combined with a slightly lower relative survival rate for those with metastatic disease. Differences in treatment are unlikely to explain the findings, although delays in diagnosing and treating patients in Denmark compared with neighbouring countries could partially explain the lower patient survival in Denmark. In conclusion, the main factor in the lower survival rate in Denmark is unfavourable stage distribution.

Small Cell Neuroendocrine Carcinoma of the Larynx

Small cell neuroendocrine carcinoma, also known as anaplastic small cell or oat cell carcinoma, is a frequently encountered bronchogenic neoplasm. Despite the fact that the embryologic origins of the larynx and the lung are the same, laryngeal manifestation of small cell neuroendocrine carcinoma is unusual, accounting for less than 0.5% of laryngeal carcinomas.1 We present the case of a 72-year-old man with small cell neuroendocrine carcinoma of the larynx, who was treated with full-course radiotherapy and achieved complete tumor remission. Subsequently, multiple liver metastases were confirmed and systemic chemotherapy was initiated. Unfortunately, the patient died 12 months after initiation of tumor-directed therapy.

Small round cell tumors of the abdomen and thorax. Role of fine needle aspiration cytologic features in the diagnosis and differential diagnosis.

To evaluate the role of cytomorphologic features in the diagnosis and differential diagnosis of small round cell tumor (SRCT) of the abdomen and thorax. During a period of six years (1985-1990), ultrasound/ computed tomography-guided fine needle aspiration cytology was performed on thoracic and abdominal/ pelvic masses in 899 cases. Slides were not available for review in 28 cases. Review of smears by one of the investigators (D.K.D.) in the remaining cases, which included 239 with intrathoracic and 632 with intraabdominal/pelvic masses, yielded 380 (43.6%) cases of malignancy. Of these, 71 (18.7%) cases were small round cell tumors. In 59 cases of SRCT the smears were found suitable for detailed assessment of cytomorphologic features. The 59 cases of small round cell tumors included 5 cases of neuroblastoma, 7 of hepatoblastoma, 4 of nephroblastoma, 1 of pulmonary blastoma, 2 of Ewing's sarcoma, 23 of non-Hodgkin's lymphoma (NHL), 15 of small cell anaplastic carcinoma (SCAC), 1 NHL/SCAC and 1 small round cell tumor (not otherwise specified). The frequencies of rosettes (60%) and filamentous/fibrillar matrix (100%) in neuroblastoma; acinar formation in hepatoblastoma (100%) and SCAC (93.3%); tubule formation in nephroblastoma (100%); lipid vacuoles (69.6%), exclusive noncohesive cells (95.7%) and lymphoglandular bodies (87%) in NHL; and nuclear molding (100%) and paranuclear blue inclusions (60%) in SCAC were significantly higher as compared to the rest of the SRCTs (P < .01 to < .0001). The various cytomorphologic features, alone or in conjunction with other cytologic features, and clinical/imaging findings are very useful in the diagnosis of specific types of SRCT.

Parameters derived from integrated nuclear fluorescence, syntactic structure analysis, and vascularization in human lung carcinomas.

Combined measurements of integrated nuclear fluorescence (INF) and vascularization were performed on surgical specimens of human lung carcinomas. Histological slides of formalin‐fixed, paraffin‐embedded tissue samples were treated with Texas Red‐labeled antibody to factor VIII and the fluorochrome DAPI. The resulting images were analyzed with an epi‐illumination fluorescence microscope and two different filter blocks. The first image displayed the vessels, and the second the DAPI‐stained nuclei of surrounding cells. The extent of vascularization was assessed by calculating the volume fraction (Vv), the surface fraction (Sv), the area, and the minimum diameter of the vessels. The INF was measured in tumour cells and lymphocytes, and was grouped according to the distance from the nearest vascular boundary into the intervals of 0–20, 21–40, 41–60, 61–80, and >80 μ. The numerical densities (Nv) as well as the percentages of S‐phase‐related tumour cell fraction (SPRF) and of tumour cells with an INF > 5C were computed. A minimum of 50 vessels and 300 tumour cells were examined. The material included 100 cases with primary lung carcinoma (39 epidermoid carcinomas, 39 adenocarcinomas, 13 large cell carcinomas, three small cell anaplastic carcinomas, and 6 carcinoid tumours). On the average, the volume density of the stroma amounts to 16.7%, and that of the vessels (Vv) to 12.8%. The minimum diameter of the intratumoral vessels is 13 μ and the measured circumference 138 μ. The numerical densities of tumour cells (lymphocytes) decrease with increasing distance from the vascular boundary from 6.3 (1.7) to 1.0 (0.1). A reduction is also seen in the percentage of the SPRF from 10.7 to 8.1%. The percentage of tumour cells with an INF > 5C, however, is positively correlated to the distance from the vascular surfaces from 34.2 to 38.2%. The measurements reveal that tumour cells are densely positioned and have an increased proportion of proliferation in the populations close to perivascular spaces, whereas chromosome abnormalities are seen more frequently, when tumour cells are located at a distance >20 μ from the vascular surfaces.

Immunoreactivity for hepatocyte growth factor/scatter factor and its receptor, met, in human lung carcinomas and malignant mesotheliomas.

Paraffin sections from 29 lung carcinomas (28 primary and 1 metastatic) and 9 pleural malignant mesotheliomas were immunostained with antisera to human hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, met. For HGF/SF, immunoreactivity was demonstrated in all 9 mesotheliomas, 9 of 12 adenocarcinomas, and 7 of 10 squamous cell carcinomas. None of seven cases of small cell anaplastic carcinoma was positive. The adenocarcinomas frequently showed enhanced luminal staining, suggesting possible secretion of HGF/SF, and this pattern of staining was also seen occasionally in bronchial epithelium adjacent to the tumour. Stromal fibroblasts also showed immunoreactivity for HGF/SF in 6/8 cases of mesothelioma but in only 3/12 adenocarcinomas, 1/10 squamous cell carcinomas, and 1/4 small cell anaplastic carcinomas. All tumours stained for met, usually strongly. The staining was mainly cytoplasmic in nature, but some plasma membrane staining was usually evident. Adenocarcinomas showed strong luminal membrane staining, as did adjacent, histologically normal bronchial epithelium. This study demonstrates the presence of HGF/SF and met in most of the tumour types described, particularly mesotheliomas, and suggests that the HGF/SF/met signalling system may play a role in the development of these tumours, either by autocrine or by paracrine mechanisms.

Prognostic relevance of detection of ligands for vertebrate galectins and a Lewis(Y)-specific monoclonal antibody

Tissue sections taken from 157 potentially curatively operated lung carcinoma patients (70 epidermoid carcinomas, 68 adenocarcinomas, 15 large cell anaplastic, and 4 small cell anaplastic carcinomas) were examined by a standardized histochemical protocol in a prospective study evaluating the extent of various types of probes to serve as prognostic indicators in lung cancer. Detailed clinical records and survival data (minimum 56 weeks, maximum 96 weeks) were correlated to the results of the histochemical reactions. The study centres on monitoring the expression of galactoside-containing epitopes in tumor cells by human, animal and plant lectins: and with a monoclonal antibody. In addition, affinity-purified subfractions of natural antibodies from human serum with preferential affinity to alpha- and beta-galactosides, respectively, were employed. Significant contributions to the estimation of the survival of patients are given by clinical parameters (pT, pN stage), number of resected and positive lymph nodes and presence of tumor metastases into specific lymph nodes (No. 5 and No. 6 right and left). With respect to the relevance of subsets of beta-galactosides, the galectin from chicken liver (CL-16) and the Le(y)-specific monoclonal antibody unveiled a negative correlation at a statistically significant level. The predictive value of binding of the animal lectin CL-16 was especially pronounced for patients with advanced tumor stages, pointing to a potential role of such lectin-reactive beta-galactosides in late tumor stages or progression.