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The role of alpha(v)beta(3) in prostate cancer progression.

Integrin alpha(v)beta(3) is involved in varied cell biological activities, including angiogenesis, cell adhesion, and migration on several extracellular matrix components. Although alpha(v)beta(3) is not typically expressed in epithelial cells, it is expressed in macrophages, activated leukocytes, cytokine-stimulated endothelial cells, osteoclasts, and certain invasive tumors. Interestingly, the adhesion and migration of breast cancer cells on bone matrix are mediated, in part, by alpha(v)beta(3). Similar to breast cancer cells, prostate cancer cells preferentially metastasize to the bone. The biological events that mediate this metastatic pattern of prostate cancer are not well defined. This review discusses the role alpha(v)beta(3) plays in prostate cancer progression, with specific emphasis on bone metastasis and on alpha(v)beta(3) signaling in prostate cancer cells. The data suggest that alpha(v)beta(3), in part, facilitates prostate cancer metastasis to bone by mediating prostate cancer cell adhesion to and migration on osteopontin and vitronectin, which are common proteins in the bone microenvironment. These biological events require the activation of focal adhesion kinase and the subsequent activation of PI-3 kinase/Akt signaling pathway.

Cell Adhesion↗

CGH analysis of ductal carcinoma of the breast with basaloid/myoepithelial cell differentiation.

2-18% of ductal carcinoma-No Special Type (NST) are reported to express basal cell keratin 14 and such tumours may have a different metastatic pattern and prognosis. We performed immunohistochemistry for cytokeratins 19 (luminal) and 14 (basal) on 92 ductal carcinoma-NST. Those tumours showing CK14 expression were further characterized by immunohistochemistry for myoepithelial cell phenotype and analysed by comparative genomic hybridization. The 7 cases of ductal carcinoma-NST exhibiting a basal cell phenotype were all grade III tumours and showed a molecular cytogenetic profile similar to more conventional myoepithelial cell carcinomas. Therefore it appears that grade III invasive ductal carcinomas contain a subset of tumours with specific morphological and cytogenetic characteristics, and probably prognosis for the patient.

Adult↗

[Pulmonary metastasis of extranodal high malignancy B-cell non-Hodgkin lymphoma of the bulbus duodeni and pylorus of the stomach].

We report a 71-year-old female patient with repeated vomitus, meteorism, epigastric pain and reflux for more than four month. She had a palpable mass in the upper abdomen and lost 7 kg of weight during the last four months. Chest X-ray showed two masses, 2 cm and 3 cm in diameter, in the left and right lower lung. A stenosing polypoid mucosal swelling in the antrum and the duodenal bulb. The pulmonal masses were biopsied under CT-guidance. Biopsy proved a high malignant B-cell non-Hodgkin's lymphoma of the stomach. The masses in the lung were identified as metastases of the gastrointestinal lymphoma. In conclusion on this tumor was an extranodal non-Hodgkin's lymphoma stadium BE IV according to Musshoff. A CHOP-chemotherapy was initiated. Restaging after three cycles of CHOP revealed a complete remission. Primary gastrointestinal non-Hodgkin's lymphomas are relatively rare neoplasms of the abdomen. Unusual and interesting in this case ist the metastatic pattern involving the lung periphery without local lymph node metastases.

Aged↗

[Results of the German studies (MAHO) for treatment of testicular germ cell tumors in children--an update].

BACKGROUND: The MAHO studies for treatment of testicular germ cell tumors in childhood and adolescence registered between 1982 and 1/2001 260 patients (pts.). Aims of the studies were: 1. Delay of chemotherapy in YST of stage I A. 2. Delay of modified lymphadenectomy for staging in I A tumors. 3. Stepwise reduction of therapy in low stage tumors but increasing therapy in tumors of metastatic pattern. Standard therapy consisted of 4 courses of vinblastine, bleomycin and cisplatin. In stage II C or higher chemotherapy included cisplatin, VP 16 and bleomycin. As salvage therapy VP16, ifosfamide and cisplatin was given. RESULTS: According to histology and stage only 75/260 pts. needed chemotherapy. Out of 140 pts. with YST 139 survived disease free according to a "watch and wait" policy. 16 of these patients (13 %) needed a delayed standard chemotherapy 6 - 60 weeks after orchiectomy. Patients with mature (40 pts.) and immature (19 pts.) teratoma were cured by orchiectomy alone. 59 pts. suffered from other malignant non-seminomatous tumors (EC, chorio, mixed tumors). 20 of these had a clinical stage I including 5 with a pathologic stage I A. 15 received adjuvant chemotherapy and all 20 pts. survived relapse-free. 22 pts. had stage II, 8 of these received salvage therapy in addition to standard chemotherapy, 21 of 22 pts. survived. 17 pts. had stage III or IV, 5 of these died despite receiving salvage therapy, 9 pts. survived in complete remission, 3 pts. had partial remission. Both patients with a seminoma (stage I) survived. In summary, the probability of disease free survival of 260 pts. is 97 % after a median observation time of 60 months. CONCLUSION: In alpha-fetoprotein producing YST tumors of clinical stage I A after semincastratio the "watch and wait" surveillance strategy is found to be optimal. Only about 13 % of these patients had to be treated by chemotherapy at a later time point and thus could be cured. For YST pts. of stages greater than stage I A and all other malignant testicular tumors in childhood effective chemotherapy exists with an overall cure rate of about 95 %. Local irradiation or staging lymphadenectomy is unnecessary.

Adolescent↗

[Cutaneous malignant melanoma of the head and neck with intermediate tumor thickness: the role of elective lymph node dissection for clinical stage I].

BACKGROUND: At present a tendency towards a more limited surgery in the treatment of clinical stage I and II melanoma exists. The controversy of elective lymph node dissections (ELND) in stage-I-melanoma with intermediate tumor thickness continues to be discussed. The sentinel lymph node biopsy may provide improved staging accuracy. METHODS: It was the aim of this study to examine whether extent of surgical treatment particularly the ELND in case of intermediate tumor thickness has prognostic significance. Metastatic pattern of these malignant melanoma were analyzed to form a basic for routine sentinel lymph node biopsy. RESULTS: No prognostic difference could be shown in clinical stage I melanoma with intermediate tumor thickness between "local excision" (no lymph node dissection) or "wait and see" (delayed lymph node dissection because of clinical suspicion) respectively and "local excision with elective neck dissection". The 5-year survival was 67 %, 67 % and 69 %. It ran to 53 % in case of therapeutical lymph node dissection as primary therapy. Occult nodal metastases occur in 15 % and "skip"-metastases in 6 %. CONCLUSIONS: No therapeutic value for ELND in clinical stage I malignant melanoma of the head and neck with intermediate tumor thickness could be shown. The low incidence of occult nodal metastases and "skip"-metastases represents the basic for sentinel lymph node biopsy.

Follow-Up Studies↗

[Capsular rupture of lymph node metastases as most significant prognostic factor in head and neck squamous cell carcinomas--Hamburg experiences].

BACKGROUND: TNM classification of squamous cell carcinomas of the head and neck contains only size and number of the lymph node metastases. The histological criterion of capsular rupture and its prognostic significance was assessed by an exact histological scheme of capsular rupture and extracapsular spread of the metastasis and was compared with N0 or lymph node metastases without capsular rupture respectively. METHODS: Incidences of distant metastases, tumor recurrences, and survival of 194 consecutive patients with squamous cell carcinomas of the head and neck were investigated. Lymph node metastases were examined by the gradual histological scheme and patients were rated according their histological diagnosis. RESULTS: The classification N0/intranodal tumor growth/extranodal tumor growth resulted in a 5-year survival rate of 74%/62%/25%. According to the classification 67%/72%/37% of the patients were without local recurrent tumor and without distant metastases were 81%/79%/48% after 5 years. CONCLUSIONS: Capsular rupture seems to contain more decisive prognostic value as the criterion of only lymphatic metastatic disease. The histological scheme allows an exact assessment of the capsular rupture or the metastatic pattern of the lymph node. Because of its prognostic significance and individual therapeutic consequences the easily reproducible criterion of capsular rupture is a useful completion to current TNM classification.

Actuarial Analysis↗

A case report of a spontaneous gastrointestinal stromal tumor (GIST) occurring in a F344 rat.

We report a case of gastrointestinal stromal tumor (GIST) that developed in a male F344 rat at week 101 of an experiment in a carcinogenicity study. Macroscopically, the primary tumor, which measured 1 cm in diameter, involved the submucosal tissue of the forestomach at the lesser curvature extending to the glandular stomach and esophagus. Histopathologically, the tumor was composed of neoplastic cells with small- to medium-sized spindle-shaped single nuclei and fibrillary cytoplasm lacking distinct cell borders. It invaded extensively into the tunica muscularis and subserosa, further extending to the lamina propria mucosa and serosal surface. A few densely proliferating portions showed a tendency to storiform pattern. Metastatic tumor nodules were found in the liver, spleen, and femur bone marrow, with multiple nodules, up to 1 cm in diameter, apparent in the liver. Immunohistochemically, diffuse, but weak cytoplasmic immunoreactivity for KIT was evident, and most neoplastic cells also exhibited strong immunoreactivity for a -smooth muscle actin and vimentin. Sparse nuclear S-100-immunoreactive cells were further observed, but none of neoplastic cells were immunoreactive for CD34, caldesmon, desmin, cytokeratin, or synaptophysin. Collectively, these features meet the criteria for a GIST, with limited potential for differentiation to smooth muscle and neural cells.

Actins↗

Two unusual cases of metastatic osteosarcoma detected by Tc-99m MDP bone scintigraphy.

Tc-99m MDP bone scintigraphy is widely used for initial staging and subsequent follow-up of patients with osteosarcoma. Two unusual cases are presented here, one with diffuse pleural metastases and one with diffuse peritoneal metastases. In one case, an abnormal bone scan was the first indication of metastatic disease. Both the metastatic pattern of osteosarcoma and the indications for bone scintigraphy are reviewed.

Adolescent↗

Lung cancer in North-West Italy: demographic and clinical trends in a hospital-based population of 1277 patients.

This study intends to assess which demographic and/or clinical characteristics of lung cancer - if any - have changed during the last two decades in an Alpine area of North-West Italy. The study was carried out on 1277 consecutive lung cancer patients seen from January 1989 to October 2002 in a single institution. A set of 33 anthropometric, clinical, physical, laboratory, radiological and pathological variables was prospectively recorded for all patients. The date of diagnosis was used to divide the study population in quartiles of diagnostic age (period I: January 1989 to May 1992, 319 patients; period II: June 1992 to September 1995, 319 patients; period III: October 1995 to May 1999, 320 patients; period IV: June 1999 to October 2002, 319 patients). Patients were carefully followed up, and their subsequent clinical course recorded. The following variables showed a significant increasing trend over the years: patients' age, female sex, rate of ex-smokers, level of education, co-morbidity (both the number and the severity of previous pulmonary and extrapulmonary diseases), weight loss, liver enzymes and blood creatinine, carcinoembryonic antigen levels and the rate of adenocarcinomas. On the other hand, performance status, stage of disease, metastatic pattern, treatment modalities and survival expectancy did not change. Therefore, no diagnostic or therapeutic improvements occurring during the last 14 years had a visible impact on patients. It may be that the 'changing face' of lung cancer masked their effects.

Adult↗

Clear cell sarcoma of the kidney: an unusual presentation and review of the literature.

PURPOSE: To describe a child with clear cell sarcoma of the kidney (CCSK) with an unusual presentation, including a primary tumor of the left kidney with metastases to the right kidney and soft tissues of the lower extremities, and to review the literature. PATIENT AND METHODS: An 8-month-old infant presented with hypertension, an abdominal mass, and soft tissue masses in the left thigh and right foot. Imaging studies revealed a large left-sided renal tumor, left paravertebral soft tissue masses, and left thigh mass. At laparotomy, a lesion was noted in the lower pole of the contralateral kidney. CCSK with metastases to the contralateral kidney and to the soft tissues of left thigh, right foot, and left paravertebral region was diagnosed on histopathologic examination. RESULTS: Multimodal oncologic treatment included surgery, chemotherapy, and radiotherapy. Three months after completion of therapy, a soft tissue lesion in the left arm and, later, soft tissue lesions involving multiple parts of the body developed. The patient died 18 months after diagnosis without clinical or radiographic evidence of bone involvement. CONCLUSIONS: In a review of the literature, CCSK is most commonly associated with bone and lung metastases. Soft tissue involvement is uncommon. Metastasis to the contralateral kidney at initial diagnosis has not previously been reported. This case represents an unusual metastatic pattern of CCSK.

Combined Modality Therapy↗

Critical care of the patient with lung cancer.

Critical care of patients with lung cancer requires a knowledge of the behavior of this malignancy and the implications of several prognostic variables. Lung cancer's location, cellular characteristics, and metastatic patterns predispose patients to many emergencies that may require critical care intervention. In this article, the author presents important background on the behavior of this malignancy, its treatment, and predicted critical care problems. Included is a discussion of complications such as spinal cord compression, superior vena cava syndrome, airway obstruction, pleural effusions, and neoplastic cardiac tamponade, with an overview of common paraneoplastic syndromes. A case study exemplifies a possible presentation and management of a patient with lung cancer and some of these complications.

Critical Care↗

Skeletal metastasis in patients with gastric cancer.

To clarify metastatic patterns, and histologic and radiologic features in skeletal metastases from gastric cancer, 48 patients were retrospectively analyzed. The mean age of the patients at the time of diagnosis of gastric cancer was 59 years. In 31 patients with a history of the radical surgery, the mean interval between surgery and diagnosis of skeletal metastasis was 14 months. The mean duration between diagnosis of skeletal metastasis and death was 60 days. Scintigraphic assessment showed that solitary osseous lesions were found in four patients, whereas the remaining 44 had multiple skeletal lesions. In 28 patients with bone-only metastases with absence of visceral metastases, a higher incidence of thoracolumbar metastases at the level nearest the stomach was found. The incidence of skeletal metastasis in each histologic type was intestinal in 19 and diffuse in 29. Radiologic examination revealed that the ratio between the presence and the absence of osteosclerosis was 1:2. Osteosclerosis was seen in three of 19 patients with intestinal type metastasis, whereas with the diffuse type 13 of 29 patients had osteosclerosis.

Adult↗

Multiple cutaneous acral metastases in a woman with breast adenocarcinoma treated with pegylated liposomal doxorubicin: incidental or aetiological association?

This paper reports the case of a 45-year-old female with histologically documented, multiple cutaneous metastases in the palmar and plantar surface of the fingers and toes originating from a breast adenocarcinoma after treatment with a docetaxel and pegylated liposomal doxorubicin regimen. The rarity of such a metastatic pattern from breast cancer and the eventual association with the chemotherapy administered are thoroughly discussed.

Antibiotics, Antineoplastic↗

Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast.

AIMS: Cytokeratin (CK) 14, a myoepithelial marker, is also expressed in a proportion of breast carcinomas. There is evidence that these tumours show a differing metastatic pattern and clinical outcome from other invasive ductal carcinomas (IDCs) and may need different management. Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC. METHODS AND RESULTS: A detailed histological review of 453 grade 3 IDCs revealed 88 (19.4%) that expressed CK14. Assessment was made independently by two pathologists using a standardized 'tick-box' proforma covering grade, architectural and cytological features. The results were analysed using logistic regression to identify features that predicted for basal phenotype. Concordance between the two pathologists was fair to good for most parameters (kappa 0.4-0.6). On multiple logistic regression, the basal phenotype was highly significantly associated with the presence of a central scar (P = 0.005), tumour necrosis (P < 0.0001), presence of spindle cells (P = 0.006) or squamous metaplasia (P < 0.0001), high total mitotic count (> 40 per 10 high-power field) (P = 0.0002) and high nuclear-cytoplasmic ratio (P = 0.0002). CONCLUSIONS: Specific morphological features are strongly associated with basal-like breast carcinoma. These could be used in routine diagnostic practice to identify this important subset of tumours.

Biomarkers, Tumor↗

Carcinoma of the tonsil with bilateral breast metastasis: a rare presentation.

With increasing local regional control and survival rates, the incidence of distant metastasis is increasing. Head and neck malignancies traditionally metastasize to the lung, liver and bone. We present a case of an elderly woman who was loco-regionally controlled after radiotherapy for carcinoma of the tonsil, but later presented with breast metastasis. To our knowledge, this metastatic pattern has never been reported in published literature. We also discuss the management of breast metastasis and the need to avoid unnecessary mastectomies in such patients.

Breast Neoplasms↗

Signet ring cell carcinoma of the breast.

A rare case of signet ring cell (SRC) carcinoma of the breast occurring in a 51-year-old female is presented. She was first admitted under the diagnosis of gastric carcinoma. Incidentally, a right breast tumor was detected and double cancer was thus suspected clinically. Concurrent right mastectomy and partial gastrectomy were performed. Histologic examination on the removed tumors revealed infiltration of numerous SRCs. The signet ring appearance of tumor cells resulted from formation of a large intracytoplasmic globule. From this unique cytologic feature along with the presence of in situ lesion in the breast tumor, it was concluded that the gastric malignancy was a sequela of metastasis of infiltrating lobular carcinoma. Wide-spread metastasis later occurred, especially on the serosal surfaces. The importance for the knowledge about the unique metastatic pattern of SRC carcinoma of the breast was emphasized.

Adenocarcinoma, Mucinous↗

Expression of vascular endothelial growth factor a, matrix metalloproteinase 9 and extravascular matrix patterns in iris and ciliary body melanomas.

PURPOSE: It was the aim of this study to assess the expression of vascular endothelial growth factor (VEGF)-A, matrix metalloproteinase (MMP)-9 and extravascular matrix patterns (EMPs) in iris and ciliary body melanomas and their correlations with histopathologic parameters. METHODS: The study was conducted on 3 iris and 15 ciliary body melanomas. All tumors were subjected to immunohistochemical techniques for VEGF-A and MMP-9 expressions, the presence of EMPs was assessed, and routine paraffin sections were stained with hematoxylin-eosin. Cell type, tumor localization, degree of pigmentation, necrosis, mitotic index, lymphocytic infiltration and sclera invasion were analyzed using light microscopy. RESULTS: The mean patient age at the time of treatment was 43 years (range 19-69, median 39.5); 10 (55.6%) patients were males and 8 (44.4%) females. Histopathological cell types were spindle cells in 55.6%, mixed cells in 16.7%, and epithelioid cell types in 27.8% of tumors. Positive reaction for VEGF-A and MMP-9 was present in 66.7 and 72.3% of the tumors, respectively. Microvascular loops and/or networks were seen in 33.4% of the tumors, with the remaining 66.7% of tumors displaying one or more of the other patterns. Metastatic disease developed in only 1 patient during follow-up. Tumor cell type, tumor size, mitotic rate, degree of pigmentation and EMPs were not correlated with metastasis. CONCLUSIONS: This study suggests that VEGF-A and MMP-9 were positive in the majority of iris and ciliary body melanomas. No correlation was found between VEGF-A and MMP-9 immunoreactivity and EMPs and occurrence of metastases in cases of anterior uveal melanoma.

Adult↗

Disseminated cutaneous nodules revealing gastric carcinoma.

A 39-year-old Japanese male presented with multiple erythematous nodules on the head, face and trunk. Further investigations revealed a Borrmann type II gastric carcinoma and identified disseminated bone metastases. No other metastases of internal organs, including the liver and lungs, were clinically detected in this stage. This metastatic pattern is quite unusual.

Adult↗