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Microsatellite instability and proliferating activity in sinonasal carcinoma: molecular genetic and immunohistochemical comparison with oral squamous cell carcinoma.

Sinonasal carcinomas arise from the respiratory epithelium that lines the nasal and paranasal cavities, and are histologically composed of either squamous or cylindrical cell carcinoma. However, molecular analysis with the purpose of distinguishing sinonasal carcinomas from other head and neck squamous cell carcinomas (HNSCCs), which arise from squamous epithelium, has been limited. Moreover, a wide range of frequency of microsatellite instability (MSI) in HNSCC has been reported. Using high-resolution fluorescent microsatellite analysis (HFRMA), we studied microsatellite alterations in 34 patients with sinonasal carcinoma. As a control, 24 oral squamous cell carcinomas were used. MSI was detected in 14 patients with sinonasal carcinoma (41%), but not in any with oral squamous cell carcinoma (p=0.002). Furthermore, in sinonasal carcinoma, 11 out of 17 (65%) T1-T3 sinonasal carcinomas demonstrated MSI, whereas only 3 out of 15 (20%) T4 tumors demonstrated MSI. Immunohistochemically, sinonasal carcinoma showed a higher MIB-1-labeling index and more frequently showed cytokeratin 18 expression when compared with oral squamous cell carcinoma. These findings suggest that sinonasal carcinoma and HNSCC have quite different molecular backgrounds regarding carcinogenesis, and the role of MSI is relatively minor in cases of advanced sinonasal carcinoma.

Adult↗

Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee.

In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes 2 types of lesion, which differ in morphology, biology and clinical features. VIN, usual type (warty, basaloid and mixed), is HPV related in most cases. Invasive squamous carcinomas of warty or basaloid type is associated with VIN, usual type. VIN, differentiated type, is seen particularly in older women with lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN, differentiated type, nor associated keratinizing squamous cell carcinoma is HPV related. The term VIN should apply only to histologically high grade squamous lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1 will no longer be used. Two categories should describe squamous VIN: VIN, usual type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and VIN, differentiated type (VIN 3, differentiated type).

Carcinoma, Squamous Cell↗

[The expression of cyclooxygenase-2 in laryngeal squamous cell carcinoma and its relationship with MVD].

OBJECTIVE: To investigate the expression of cyclooxygenase-2 in laryngeal squamous cell carcinoma and the correlation with tumor angiogenesis. METHOD: The COX-2 and FVIII of 42 cases of laryngeal squamous cell carcinoma were detected by immunohistochemical SABC method,and the correlation between the expression rates, clinical significance and microvessel density(MVD) was analyzed. RESULT: The positive rate of COX-2 in laryngeal squamous cell carcinoma tissues and adjacent normal tissues were 71.43% and 19.05% respectively. The expression of COX-2 were not associated with age, sex, tumor site and T stage. The tumors of grade III approximately IV showed a higher COX-2 expression than tumors of grade I approximately II did and the expression of COX-2 in the cervical lymph node metastasis group was higher than that in the non-metastasis group. The expression of COX-2 was closely associated with microvessel density(MVD) of laryngeal squamous cell carcinoma. CONCLUSION: The expression of COX-2 may play a crucial role in the carcinogenesis and development of laryngeal squamous cell carcinoma and cervical lymph node metastasis in patients with laryngeal squamous cell carcinoma. COX-2 may be a important factor in tumor angiogenesis.

Adult↗

[Expression of tumor suppressor gene PTEN, PIP3 and cyclin D1 in oral squamous cell carcinoma and their correlations].

OBJECTIVE: To detect the expression of PTEN, PIP3 and cyclin D1 in oral squamous cell carcinoma and precancerous lesions and analyze their correlation. METHODS: Immunohistochemistry SP method was used to detect the expression of PTEN, PIP3 and cyclin D1 in 63 cases of oral squamous cell carcinoma, 29 cases of simple hyperplasia, 33 cases of dysplasia, and 25 cases of normal oral mucosa. RESULTS: The negative or low expression of PTEN in oral squamous cell carcinoma was 25%, which was remarkably lower than that in other groups. The positive expression of PIP3 in simple hyperplasia, dysplasia and oral squamous cell carcinoma was 66%, 64%, and 76% respectively, which were much higher than those in normal oral mucosa. The positive expression of cyclin D1 in oral squamous cell carcinoma was 49%, which was significantly higher than that in other groups. The negative correlation between PTEN with PIP3, cyclin D1 and the positive correlation between PIP3 and cyclin D1 were observed. CONCLUSIONS: PTEN may play a role in the oncogenesis of oral squamous cell carcinoma, and PTEN may down-regulate the expression of PIP3, and then down-regulate the expression of cyclin D1, which leads to the suppression of cell growth.

Carcinoma, Squamous Cell↗

[The characteristics of proliferation activity in squamous metaplasia and reserve cell hyperplasia of uterine cervix].

The aim of our study was to investigate the characteristics of proliferation activity in squamous metaplasia and reserve cell hyperplasia of uterine cervix. Four groups of patients were selected: 1st group--34 reproductive patients with reserve cell hyperplasia, 2nd group--21 reproductive patients with squamous metaplasia, 3rd group--12 postmenopausal patients with reserve cell hyperplasia, 4th group--29 postmenopausal patients with squamous metaplasia. These groups included the patients with and without infections. Cervical biopsies were studied by immunohistochemistry using anti-Ki-67 monoclonal antibody. Ki-67(+) reserve cells were counted in reserve cell hyperplasia. Ki-67(+) squamous cells were counted in squamous metaplasia. The results showed that in both squamous metaplasia and reserve cell hyperplasia the number of Ki-67(+) cells, i.e. the intensity of proliferation is depended on the co-existence of infection, as well as on the age of the patient. These data are important in the complex treatment of cervical pseudoerosions.

Adult↗

Expression of p53 in premalignant and malignant squamous epithelium.

Using three antibodies (JG8, CM-1 and 1081) directed to the p53 protein, strong positivity was found in 16/47 (34.0%) of mucosal squamous cell carcinomas of the head and neck and in two squamous carcinoma cell lines (LICR-LON- HN5 and HN6Rr). The presence of the mutant p53 was confirmed in the cell lines as substitutions in exon 7 (codon 238, TGT greater than AGT) and exon 5 (codon 152, CCG greater than CTG) respectively. Positive staining was seen only in the undifferentiated cells and progressively lost as the cells keratinized, both in the tumour specimens and in the cell lines. Similar results were seen in areas of dysplasia, well removed from the site of the primary tumour. Staining of epidermal lesions showed positivity in 2/12 (16.6%) cases of Bowen's disease, 0/12 (0.0%) cases of solar keratosis, 0/10 (0.0%) basal cell carcinomas and in 3/20 (15.0%) squamous cell carcinomas. These results are discussed in relation to the multifocal origin of squamous cell carcinomas, the role of p53 mutations in squamous cell carcinomas from different sites and the significance of the 'basal' distribution of p53 as a normal growth regulator. The possible significance of the distribution of p53 in squamous epithelium as it relates to papilloma virus infection is also considered.

Amino Acid Sequence↗

Squamous cell carcinoma of the uterine cervix--a review with emphasis on prognostic factors and unusual variants.

Although the incidence of squamous cell carcinoma of the cervix has declined in recent years, it remains the most common type of cervical cancer in our society. In this review, the salient pathologic features of squamous cell carcinoma are discussed. Early invasive, International Federation of Gynecology and Obstetrics (FIGO) stage la carcinoma has been a source of controversy in diagnosis and therapy for many years. Specific requirements must be met in order to make this diagnosis. Most importantly, the cervical conization specimen must be handled properly, so that the features of tumor dimensions, vascular involvement, and completeness of excision can be correctly evaluated. Important diagnostic and prognostic pathologic findings of early invasive carcinoma are discussed. The risk of lymph node metastasis in lesions with depths of invasion up to 3 mm is less than 1%. This risk increases significantly with deeper levels of invasion. In the area of frankly invasive squamous cell carcinoma of the cervix, certain pathologic features have been shown to be clinically relevant. These include the extent of local disease, cell type, and the presence of vascular or lymphatic invasion. Regarding cell type, it is critical to distinguish between poorly differentiated small cell squamous carcinoma and small cell undifferentiated carcinoma, as the prognosis for these tumors may differ. Finally, several rare but pathologically distinct variants of squamous cell carcinoma of the cervix are reviewed, with emphasis on differential histologic features. As they often have different natural histories than typical squamous cell carcinoma, correct diagnosis of these lesions is vital.

Carcinoma, Papillary↗

[Surgical experience of bronchogenic early squamous cell carcinoma detected by sputum cytology in lung cancer screening].

Eighty-one patients of roentgenologically occult lung cancer (all men, and squamous cell carcinoma) were detected by sputum cytology in lung cancer screening of "Miyagi Program". Sixty-seven patients were resected surgically, and sixty-four of them underwent absolutely curative resection. In fifty-six patients, carcinoma did not penetrate the bronchial wall, and all of them were free from lymph node involvement. In eleven patients, carcinoma penetrated the bronchial wall, and three of them were proved to have lymph node involvement. For that reason, carcinoma which did not penetrate the bronchial wall and was free from lymph node involvement, was defined as early squamous cell carcinoma. Fourty-two early squamous cell carcinoma were located on segmental or more proximal bronchi, but twelve were located on subsegmental or more peripheral bronchi. Five-year survival of fifty-six patients with early squamous cell carcinoma were 91.8%, seven of fifty-six early squamous cell carcinoma patients were multicentric, which were detected synchronously in four cases, postoperatively in two cases, and both synchronously and postoperatively in one case. Two of three postoperatively detected cases were resected surgically and alive without cancer. These results indicate the validity of surgical treatment for roentgenologically occult squamous cell carcinoma. As the most serious prognostic problem is multicentricity, careful localization of primary lesion and postoperative intensive follow-up should be considered.

Aged↗

Monocyte killing of human squamous epithelial cells: role for thrombospondin.

Human peripheral blood monocytes maintained in culture for 18 h were examined for killing of normal human keratinocytes and squamous carcinoma cells. Keratinocytes grown under conditions which maintain the undifferentiated state were highly sensitive to killing but these cells became resistant to killing after induction of differentiation. A line of squamous carcinoma cells obtained from an undifferentiated tumor (designated as UM-SCC-11B) was sensitive to killing while a second line obtained from a more well-differentiated tumor (designated as UM-SCC-22B) was resistant. Several observations suggested that interaction of monocytes with the squamous epithelial cells was mediated, in part, through thrombospondin (TSP). Monocytes synthesized TSP and were positive by immunofluorescence for surface TSP. The normal and malignant squamous epithelial cells also expressed surface TSP as well as unoccupied TSP receptors and our previous studies have shown that both TSP and its receptor are much more prominently displayed on the undifferentiated cells than on the differentiated cells. A series of anti-TSP monoclonal antibodies inhibited killing. These included an antibody directed against the Mr 25,000 NH2-terminal region of the molecule which has heparin-binding activity and three antibodies the epitopes of which lie within the Mr 140,000 non-heparin-binding fragment of TSP. High concentrations of exogenously added TSP as well as the recombinant form of the heparin-binding domain from the TSP molecule also partially inhibited killing while laminin and fibronectin were ineffective. Taken together, these data suggest that TSP and TSP receptors on monocytes and squamous epithelial cells play a role in monocyte-mediated killing of the squamous epithelial cells.

Antibodies, Monoclonal↗

Abnormal responsiveness of nephrogenous cyclic AMP excretion following intravenously administered calcium in normocalcaemic squamous cell cancer patients.

The renal response to calcium infusion was compared in ten normocalcaemic patients with squamous cell cancer and in ten normocalcaemic patients with adenocarcinoma. Both groups were comparable with regard to tumour load, renal function, magnesium and 25-hydroxyvitamin D levels. After injection of 3 mg elementary Ca/kg BW nephrogenous cAMP excretion fell significantly in the group of adenocarcinoma patients (1.74 +/- 1.14 nmol/dl GF vs. 2.81 +/- 1.39 nmol/dl GF; P less than 0.01) and TmPO4/GFR rose significantly at 60 and 120 min. No fall in NcAMP excretion was observed in the group of squamous cell cancer patients (2.18 +/- 0.84 vs. 2.24 +/- 0.84 nmol/dl GF; NS) and TmPO4/GFR remained unchanged. Three of ten patients with squamous cell cancer showed a paradoxical rise in NcAMP excretion following calcium administration. The other seven patients with squamous cell cancer showed a decline in NcAMP excretion (delta NcAMP) which was significantly less than in the ten patients with adenocarcinoma (0.52 +/- 0.16 vs. 1.23 +/- 0.74 nmol/dl GF; P less than 0.05). Increased phosphaturia was observed in three of ten patients with squamous cell cancer after calcium was administered. This also occurred in the presence as well as in the absence of a paradoxical activation of the adenylate cyclase system. It is concluded that the abnormal NcAMP response to calcium-infusion in normocalcaemic squamous cell cancer patients might be due to the presence of a non-suppressible PTH-like substance in these patients.

Adenocarcinoma↗

Squamous cell carcinoma of the skin. Accuracy of clinical diagnosis and outcome of follow-up in Australia.

The accuracy of the clinical diagnosis of 1292 non-melanotic skin tumours that were submitted to a private pathology service in 1980-1981 was determined. The clinical diagnosis that was written on the pathology slip which was submitted with the tumour was correlated with the histological diagnosis and the type of medical practitioner submitting the lesion. The clinical diagnosis was most accurate in the case of basal cell carcinoma; dermatologists most often reached this diagnosis correctly. For squamous cell carcinoma, although most frequently the lesions were diagnosed correctly clinically by dermatologists, their clinical diagnosis was confirmed in only 51% of cases. On average, 36% of squamous cell carcinomas were diagnosed clinically as basal cell carcinomas. The clinical course of 299 patients with a total of 305 squamous cell carcinomas that were selected from the squamous cell carcinomas that were submitted in 1980-1981 was traced. Four tumours (1.6%) which occurred in sun-exposed areas of the body metastasized, and 18 (7.5%) recurred locally. We conclude that those non-melanotic skin tumours which have the most potential to metastasize (squamous cell carcinomas) are those which are most poorly diagnosed clinically. It is recommended that patients with non-melanotic skin cancers should undergo biopsy as a routine to confirm the clinical diagnosis. Those who have a squamous cell carcinoma removed should be followed up for at least two years after the initial treatment.

Adult↗

Involucrin in lung tumors. A specific marker for squamous differentiation.

Involucrin is a precursor of the cross-linked envelope protein or marginal band present in human stratum corneum. This study uses immunohistochemical techniques for localization of involucrin in histologic sections from 91 lung tumors in order to evaluate the usefulness of involucrin as a tumor marker in lung neoplasms. Although involucrin is absent from bronchial epithelium, it is expressed in cultured tracheal epithelial cell colonies and in bronchial mucosa with squamous metaplasia. Involucrin was present in all 25 cases of squamous and adenosquamous carcinoma. Staining was focal in 12 cases of squamous cell carcinoma and was most marked in the larger neoplastic cells in the center of squamous cell nests. Only two of 20 cases of adenocarcinoma revealed focal staining for involucrin, and these cases may represent adenosquamous variants. Six of 12 cases of large cell undifferentiated carcinoma stained for involucrin, indicating squamous differentiation, and seven cases of malignant mesothelioma were negative. Isolated involucrin-positive cells were present in two of 16 cases of small cell anaplastic carcinoma and one of 11 carcinoid tumors, identifying variants of neuroendocrine tumors with dual differentiation. Patterns of localization of involucrin in paraffin and frozen sections were compared with staining for cytokeratins in parallel sections. Immunohistochemical localization of involucrin comprises a specific marker for squamous differentiation in lung tumors.

Adenocarcinoma↗

Cell-mediated cytotoxicity in preinvasive and invasive squamous cell carcinoma of the cervix.

Cell-mediated immunity was tested by coincubation of target cell line (2043) of human squamous cell carcinoma and peripheral blood leukocytes (PBL) of 22 patients with squamous cell neoplasia of the uterine cervix, 9 patients with other tumors, and 9 normal females. The percentage of cell reduction in mild dysplasia was 90.1 +/- 6.8% (.001 less than P less than .005), in moderate dysplasia was 91.1 +/- 6.4% (.001 less than P less than .005), in severe dysplasia was 91.6 +/- 15.6% (P less than .001), in carcinoma in situ was 85.0 +/ 2.6% (P less than .001), and in invasive squamous cell carcinoma of the cervix was 85.0 +/- 6.9% (P less than .001). Peripheral blood leukocytes of patients with squamous neoplasia did not show any significant cytocoxicity against cell line SKOV-3, developed from an ovarian adenocarcinoma, nor did the PBL of patients with "other tumors" show any significant cytotoxicity against cell line 2043. This study shows that even in early stages of preinvasive squamous cell carcinoma of the cervix, the PBL are sensitized against the neoplastic process, confirming that different stages of cervical intraepithelial neoplasia and invasive squamous cell carcinoma are different intensities of the same biologic process.

Antigen-Antibody Reactions↗

Undifferentiated, nonkeratinizing, and squamous cell carcinoma of the nasopharynx. Variants of Epstein-Barr virus-infected neoplasia.

Nasopharyngeal carcinoma (NPC) samples of distinct histological types, including squamous cell carcinoma (WHO type 1), nonkeratinizing carcinoma (WHO type 2), and undifferentiated carcinoma (WHO type 3), were analyzed for Epstein-Barr virus (EBV) infection and gene expression by using in situ and biochemical techniques. The EBV-encoded RNAs (EBER) were detected in situ in most tumor cells of all three WHO types of NPC. In foci of squamous differentiation and keratinization within less differentiated NPC and throughout the expanse of well differentiated squamous cell carcinoma, EBER expression was less abundant. Latent membrane protein, an EBV-encoded membrane protein, was detected in 72% (36/50) of all NPC and 67% (6/9) of the cases of squamous cell carcinoma. The EBV genomes were present as clonal episomal forms, without detectable linear viral DNA, in all cases of squamous cell carcinoma analyzed. Polymerase chain reaction amplification of cDNA detected EBV transcription for Epstein-Barr nuclear antigen 1, latent membrane proteins 1 and 2, and BamHI A in all samples, indicating that all forms of NPC express the same EBV genes. These results reveal that EBER expression is significantly decreased in areas with squamous differentiation and confirm that all types of NPC, regardless of histological type or differentiation contain clonal episomal EBV genomes, express specific EBV genes and are a clonal expansion of EBV-infected cells.

Base Sequence↗

Concurrent p53 expression in bronchial dysplasias and squamous cell lung carcinomas.

We analyzed the p53 protein immunohistochemically in bronchial dysplasias or squamous cell carcinomas in situ and in squamous cell lung carcinomas occurring in the same patients. The polyclonal antibody used (CM-1) is directed against the wild-type p53 protein, but also recognizes the mutated p53 in formalin-fixed and paraffin-embedded sections. To study the integrity of basement membranes (BMs) and the possible invasion of the dysplastic epithelium, immunostainings for the BM proteins laminin and type IV collagen were used. Nine of the 17 dysplasias showed p53 protein expression (53%); it was significantly more often seen in severe dysplasias and carcinomas in situ than in mild or moderate dysplasias (P = 0.04). The p53 antigenicity was generally located in the basal part of the epithelium. The BMs beneath mildly dysplastic epithelia were continuous. In contrast, those under moderately or severely dysplastic epithelia showed occasional disruptions. p53 protein expression was also found in dysplastic epithelium above a continuous BM suggesting an ominous process before signs of invasion. Twelve of the 17 squamous cell carcinomas showed p53 protein expression (71%). There was a significant concurrent p53 expression in bronchial dysplasias and their related squamous cell carcinomas (P = 0.009), so that all nine cases of p53 positive bronchial dysplasia also showed p53 positivity in the associated squamous cell carcinomas. These findings indicate that p53 protein expression is possible in premalignant bronchial lesions, and suggests that the p53 expression could, at least in some cases, be an early event in the development of a squamous cell carcinoma of the lung.

Aged↗

Diffuse pagetoid squamous cell carcinoma in situ of the esophagus: a case report.

BACKGROUND: In Western countries, esophageal squamous cell carcinoma is usually advanced at presentation and is rarely diagnosed in situ. The authors studied an in situ squamous cell carcinoma that occupied the entire mucosa of a 9 cm length of esophagus, causing dysphagia for solid food in a woman aged 68 years. METHODS: The esophagectomy specimen contained a circumferential region of depressed tan mucosa in the middle and lower thirds, bordered above and below by normal squamous mucosa, without ulcer, stricture, or mass. The entire lesion was submitted for histology and evaluated with immunostains for cytokeratins and markers of Paget's cells, p53 mutation, and proliferation. RESULTS: The lesion involved 45 cm2 of mucosa. Large, atypical cells with frequent mitoses occupied the basal layers of the squamous epithelium and were often separated from more superficial maturing cells by acantholysis. Pagetoid spread of tumor cells into nonneoplastic surface and gland duct epithelium was prominent. The tumor cells expressed cytokeratins of low molecular weight, p53 gene product, and proliferating cell nuclear antigen (PCNA), but lacked markers usually seen in Paget's cells in the breast or vulva. No invasion was evident. CONCLUSIONS: This extensive in situ squamous cell carcinoma of the esophagus resulted from pagetoid spread of tumor cells. These cells had a phenotype suggestive of origin from primitive epidermal stem cells and also had overexpressed p53 and PCNA, but they lacked the capacity to penetrate the basement membrane. Flat, erythematous areas of esophageal mucosa seen during endoscopy could represent early squamous cell carcinoma and should be biopsied.

Aged↗

p53-independent expression of p21waf1/cip1 in preinvasive and invasive squamous neoplasms of the uterine cervix.

Although mutations of the p53 gene are the most common genetic alteration in human tumors, they are relatively rare in cervical carcinomas, possibly because human papillomaviruses of the oncogenic type encode for an oncoprotein that leads to the ubiquitin-mediated destruction of p53. An important mediator of p53-induced cell-cycle arrest is p21waf1/cip1, and although several studies evaluated invasive and preinvasive cervical lesions for p53 expression, none has studied expression of this important downstream effector. We examined normal cervical squamous epithelium, squamous cell carcinomas, and a range of preinvasive cervical lesions for expression of p53, p21waf1/cip1, and the proliferation-associated antigen, Ki-67, by immunohistochemical analysis. p53 expression was absent in normal squamous epithelium and all dysplasias regardless of severity, consistent with the presence of predominantly wild-type p53. Invasive carcinomas were mostly negative but contained occasional small nests of cells immunoreactive for p53. p21waf1/cip1, on the other hand, was expressed in all normal squamous epithelium and all preinvasive and invasive lesions. In normal squamous epithelium, the basal and immediate parabasal layers were negative, with the early differentiating layers positive. Expression was increased in dysplasias compared with normal squamous epithelium, both in number of immunoreactive nuclei and intensity of staining. The highest expression was seen in high-grade dysplasias and invasive carcinomas. Ki-67 expression also increased with increasing severity of the lesion, but p21waf1/cip1 and Ki-67 seemed to be expressed in different cells, a fact that was confirmed by double immunohistochemical staining for these two proteins on the same sections. This paradoxical increase in p21waf1/cip1 expression and mutually exclusive expression might be related to the role of p21waf1/cip1 in differentiation.

Adult↗

Immunohistochemical evaluation of tumour angiogenesis in adenocarcinoma and squamous cell carcinoma of lung.

Experimental studies revealed that growth and expansion of solid tumours depend on angiogenesis. Angiogenesis is very important factor for neoplastic metastasis. The presence of the metastasis is an ominous prognostic factor for many tumours, also for lung cancer. Studies of tumour microvessel density in resected non-small lung cancers have not given convincing data about value of angiogenesis. Only few reports regarded the association with angiogenesis in different histological types in lung carcinoma. Samples of 35 adenocarcinomas and 41 squamous cell resected, primary lung carcinomas were studied. Paraffin sections of tumours were stained immunohistochemically by antibody against endothelial marker CD34. Angiogenesis intensity was measured in the areas of the most active fields of tumour neovascularization. Microvessel density (MD) was higher in adenocarcinoma comparing to squamous cell cancer, but the difference was not statistically significant (p = 0,095). The groups of various stage of extension of disease in each histological type were compared-MD correlated with lymph node metastasis (p = 0,003) in the adenocarcinoma, whilst in squamous cell can cer differences between various groups of nodal involvement were not statistically significant (p = 0,53 and p = 0,22 respectively). Our results suggest that more intensive angiogenesis in adenocarcinoma could be more important factor for metastasis of adenocarcinoma than for squamous tumours. In the latter group angiogenesis may be more important for growth of squamous cell cancers, while the spread of squamous tumours may depend on other mechanisms.

Adenocarcinoma↗