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Expression of MMP-9, TIMP-1, CD-34 and factor-8 as prognostic markers for squamous cell carcinoma of the tongue.

Squamous cell carcinoma (SCC) of the tongue is characterized by an unpredictable course, ranging from relatively benign to a high degree of locally aggressive growth and metastasis. Treatment guidelines have been developed according to TNM stage, but they do not always accurately predict clinical outcome. The aim of the present study was to evaluate the expression of the matrix metalloproteinases (MMPs) that degrade the extracellular matrices, their inhibitors (TIMPs), and angiogenic factors (factor-8 and CD-34) in tumor cells and to correlate these findings with the clinicopathological features and patient outcome. Tissue specimens from 23 patients with primary SCC of the tongue were immunohistochemically stained for these markers. High expressions of MMP-9 and TIMP-1 were detected in 60.9% and 65.2% of the specimens, respectively. Tumor invasion to adjacent muscle, lymph node metastasis, and disease status at the end of follow-up were positively correlated with the microvessel count using the CD-34 marker, but not with high expression of MMP-9 or TIMP-1. Expression of MMP-9 and TIMP-1 fails to predict aggressiveness in SCC of the tongue. However, the degree of vascularization in tumor tissue is indicative of disease aggressiveness and might be used as a basis for patient selection for more intensive therapy.

Adult↗

Distributions of tegafur in tissues of gastric adenocarcinoma patients: tissue uptakes and concentrations in plasma after oral and rectal administrations.

Fifty-one gastric adenocarcinoma patients were divided into two groups, according to the route of administration of the anticancer drug. One group was given FT-207 (tegafur, an enteric coated granule) orally and the other group, FT-207 in the form of a suppository. Blood and tissue concentrations of the drug were examined after a three-day administration of 750 mg at 09.00 and 21.00 hours. There were no significant differences between the two groups with respect to the concentrations of FT-207 and its metabolite 5-FU in the tissues. Levels of 5-FU in the excised tumor averaged 0.256 and 0.160 micrograms/g, in oral and rectal administrations, respectively, and levels in normal lymph nodes averaged 0.174 and 0.179 micrograms/g, respectively. The difference in 5-FU levels between normal and tumor tissues was statistically significant (P less than 0.05).

Adenocarcinoma↗

The role of fine-needle aspiration cytology in the evaluation of metastatic clear cell tumors.

BACKGROUND: Clear cell tumors (CCTs) occur as primary neoplasms in a number of anatomic sites. Due to their overlapping morphologic features, these tumors can be challenging for the cytologist, particularly when they present as metastatic lesions. METHODS: Forty-nine fine-needle aspirations (FNA) of metastatic CCTs from 46 patients (age range, 29-87 years; mean, 64 years) were reviewed retrospectively. In addition to the routine smears and cell block preparations, ancillary studies were performed in selected cases. Clinical and/or histologic follow-up was obtained for all patients. RESULTS: The sites of the 49 FNAs were the lung (12 cases), lymph nodes (9 cases), liver (7 cases), bone (7 cases), soft tissue (4 cases), pelvis (2 cases), adrenal gland (2 cases), pancreas (1 case), thyroid (2 cases), peritoneum (2 cases), and vagina (1 case). Twenty-seven patients had a previous history of a CCT and the FNA material in these cases was consistent with a metastasis. The primary anatomic sites in these cases were the kidney (20 cases), ovary (2 cases), salivary gland (1 case), and cervix (1 case). On light microscopy, these tumors had a similar appearance and often were indistinguishable. Nineteen patients did not have a prior history of malignancy; 12 of these patients had a concurrent renal mass and the diagnosis of metastatic renal cell carcinoma was made. The anatomic site of origin of seven of the ten remaining tumors (kidney [2 cases], lung [2 cases], ovary [1 case], germ cell [1 case], and endometrium [1 case]) was established through immunocytochemical studies of cytologic material and clinical follow-up. CONCLUSIONS: FNA plays an important role in the diagnosis of metastatic CCT. Cytologic examination, ancillary studies, and clinical information can establish the anatomic site of origin in the majority (95%) of cases, precluding the necessity of obtaining additional tissue. Cancer (Cancer Cytopathol)

Adenocarcinoma, Clear Cell↗

The histologic response of soft tissue sarcoma to radiation therapy.

Twenty-seven patients with soft tissue sarcoma had preoperative radiotherapy, limb-sparing marginal surgical resection and whole-mount tumor histologic analysis. Incisional biopsy specimens before radiotherapy were reviewed for tumor type, grade, and extent of necrosis. Preoperative radiotherapy was given in either of two regimens: 13 patients received a mean total dose of 5250 cGy in one daily 180 to 200 cGy fractions and 14 patients a mean total dose of 4770 cGy in two daily fractions of 180 to 200 cGy separated by 4 hours. Twenty-one specimens had at least 80% necrosis or severely altered cells, a 3+ to 4+ response. Grade and size of the tumor appeared to be indicators of response to treatment rather than histologic type. Three of five patients (60%) with Grade 1, eight of 11 patients (73%) with Grade 2 lesions, and ten of 11 patients (91%) with Grade 3 tumors had 80% or greater necrosis or severely altered cells. For tumors 10 cm or less in greatest diameter, the 3+ to 4+ histologic response was seen in 12 of 14 patients (86%) whereas for lesions greater than 10 cm, this response was observed in nine of 13 patients (69%). For patients with Grade 2 or 3 soft tissue sarcoma, 13 of 14 patients (93%) treated with two fractions per day and two of four patients (50%) receiving one fraction per day exhibited significant response. All six patients treated twice daily for lesions greater than 10 cm had 3+ to 4+ histologic response compared to three of seven (43%) patients treated once per day. Therefore, grade and size of soft tissue sarcoma are important predictors of response to radiotherapy and preoperative twice daily radiotherapy may more likely permit the conservative surgical excision of sarcomas of borderline resectability.

Adolescent↗

Proteus syndrome: an update.

Proteus syndrome is a complex disorder consisting variably of disproportionate, asymmetric overgrowth of body parts; cerebriform connective tissue nevi; epidermal nevi; vascular malformations of the capillary, venous, and lymphatic types; and dysregulated adipose tissue. Serious complications may ensue, such as pulmonary embolism, cystic lung disease, and various neoplasms. Somatic mosaicism, lethal in the nonmosaic state, is the best working hypothesis. Although Proteus syndrome data are consistent with this hypothesis, it has not been proven. The etiology is unknown to date. Diagnostic criteria are emphasized because misdiagnosis of Proteus syndrome is common. Finally, evaluation and management are discussed.

Diagnosis, Differential↗

Fatty changes and metastases in axillary lymph nodes.

A variety of pathological changes with clinical and prognostic significance is described in axillary lymph nodes removed at mastectomy. We studied 572 lymph nodes removed from 43 women and 1 man during a radical or modified radical mastectomy performed for carcinoma of the breast. We found that in about one-third of the specimens some degree of fat infiltration, or changes, was present; metastases were found in either fatty or nonfatty lymph nodes. We conclude that the presence of fat in axillary lymph nodes does not influence implantation of tumor cells from a primary carcinoma of the breast and has to be reported as an anatomic variant.

Adipose Tissue↗

[Observations on tumor-associated fibrinolysis in human breast-cancer (author's transl)].

In 30 cases of breast-cancer, including 24 primary cases, the tumor-associted fibrinolysis was investigated using agar plate method. In 60% of the tissue sample fibrinolytic activity was found. No activity could be detected in the remaining 40%. There was evidence of a positive correlation between tumor-associated fibrinolysis and tumor size as well as the rate of axilla metastases. Among the fibrinolytic active cases there was a disproporionate number of adenocarcinoma, whereas in the inactive collective the solid and scirrhous carcinoma prevailed. There was no relation between the tumor-associated fibrinolysis and the percentage of tumor cells in the tissue. The firbinolytic inactive tumors showed a better histopathological adaptation to the surrounding tissue than the active ones. There was less small-cell infiltrate in the stroma of the fibrinolytic active tumors than in the inactive cases. No significant difference was found in the form of growth and the occurence of fibre structure. For clinical assessment a longer period of observation and a larger study are necessary.

Adenocarcinoma↗

Fat clearance method versus manual dissection of lymph nodes in specimens of rectal cancer.

It is essential to submit all lymph nodes from specimens of rectal cancer for histological examination. In a prospective study we compared the traditional method of dissection with the fat clearance technique in 20 operative specimens of rectal cancer. There was no significant difference in the lymph node harvest obtained by either method. The fat clearance technique resulted in a modest saving in dissection time (mean 4 min), but was expensive (pounds 14.00 per specimen) and resulted in an unacceptable reporting delay (mean 3 days). The manual method was cheaper, as effective in identifying nodes and enabled much quicker reporting.

Adipose Tissue↗

Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate.

The aim of the present phase I/II study was to evaluate the safety, immune responses and clinical activity of a vaccine based on autologous dendritic cells (DC) loaded with an allogeneic tumor cell lysate in advanced melanoma patients. DC derived from monocytes were generated in serum-free medium containing GM-CSF and IL-13 according to Good Manufacturing Practices. Fifteen patients with metastatic melanoma (stage III or IV) received four subcutaneous, intradermal, and intranodal vaccinations of both DC loaded with tumor cell lysate and DC loaded with hepatitis B surface protein (HBs) and/or tetanus toxoid (TT). No grade 3 or 4 adverse events related to the vaccination were observed. Enhanced immunity to the allogeneic tumor cell lysate and to TAA-derived peptides were documented, as well as immune responses to HBs/TT antigens. Four out of nine patients who received the full treatment survived for more than 20 months. Two patients showed signs of clinical response and received 3 additional doses of vaccine: one patient showed regression of in-transit metastases leading to complete remission. Eighteen months later, the patient was still free of disease. The second patient experienced stabilization of lung metastases for approximately 10 months. Overall, our results show that vaccination with DC loaded with an allogeneic melanoma cell lysate was feasible in large-scale and well-tolerated in this group of advanced melanoma patients. Immune responses to tumor-related antigens documented in some treated patients support further investigations to optimize the vaccine formulation.

Adult↗

Targeting chemotherapy for intrahepatic periductal lymphatic invasion by mitomycin C adsorbed to activated charcoal in hepatic hilar bile duct cancer.

A new dosage form of anticancer agent, mitomycin C adsorbed to activated charcoal (MMC-AC), was evaluated in the rabbit model of hepatic hilar bile duct cancer. The model was produced by inoculation of VX2 cells into the wall of the hepatic hilar bile duct. Histologic examination revealed that the mode of spreading of VX2 cells in the model closely resembles that of human bile duct cancer. On the other hand, selective accumulation of MMC-AC into the lymphatic vessels around the intrahepatic bile duct was observed after its injection into the hepatic hilum in rabbits. To assess the anticancer effect, 1 ml of MMC-AC was injected into the bile duct wall near the VX2 tumor. The numbers of lymphatic vessels where necrosis of VX2 cells was observed in one-third or more were 34 of 103 vessels 0.5 cm away from the tumor, 23 of 80 vessels 1.5 cm away, and 9 of 67 vessels 2.5 cm away. We believe that the injection of MMC-AC into the hepatic hilum can be effective adjuvant therapy for hepatic hilar bile duct cancer.

Animals↗

Diagnostic imaging techniques in mediastinal malignancies.

Mediastinal masses occur in both men and women of every age, and close to half of affected patients are asymptomatic. Screening of asymptomatic persons is not economically feasible. Symptomatic patients should be evaluated initially with posteroanterior and lateral chest radiographs. Additional imaging techniques may be required in patients suspected of having a mediastinal mass, when there is a questionable abnormality seen on chest radiographs or when local or systemic symptoms suggest a mediastinal mass. These techniques include oblique views, over-penetrated radiographs, and fluoroscopy of the chest. Computerized tomography of the chest is the imaging modality of choice for further assessment of a mediastinal mass. It can also be an important adjunct in radiotherapy portal planning. The use of other imaging modalities depends on the location of the tumor, the equipment available, and the expertise of local radiologists. In following up treated patients for disease recurrence, periodic chest radiographs are usually sufficient. Computerized tomography scans, because of their expense, should only be obtained as a baseline after completion of therapy or in patients with a suspected relapse.

Humans↗

[Clear cell sarcoma (malignant melanoma of soft tissues) of the calf ].

Clear cell sarcoma (malignant melanoma of soft parts) is a rare malignancy that is found in the young adult, and is generally located in the extremities of the limbs. In this study, a new case has been reported in a 24-year old male with no previous history of cutaneous melanoma. The tumor consisted of fusiform or round cells with clear or granulocytic cytoplasm and vesicular nuclei. The patient was treated by surgical resection of the tumor and postoperative radiotherapy. Eight years later, metastatic nodes were detected in the inguinal region. The histogenesis of this tumor has not yet been determined, and it poses a diagnostic problem for pathologists as it can be mistaken for a malignant metastatic cutaneous melanoma.

Adult↗

E cadherin expression in normal and neoplastic canine mammary gland.

The epithelial intercellular adhesion molecule, E cadherin, was evaluated immunohistochemically in a series of normal and malignant neoplastic canine mammary glands. The normal glands showed strong immunolabelling at the intercellular borders of all the ductal cells. Tubular and papillary mammary adenocarcinomas had reduced intercellular E cadherin positivity with "heterogeneous" or "cytoplasmic" distribution. Solid and squamous cell carcinomas were negative. These results suggest that reduced expression and abnormal distribution of E cadherin may be related to the differentiation grade of these neoplasms.

Animals↗

Fibrosis as in indication of time in infiltrating breast cancer and its importance in prognosis.

The histological grading of tumours according to their intrinsic malignancy is very important in the prognosis of breast cancer but within each grade the ultimate prognosis depends mainly on the age of the tumours.We have shown that tumour fibrosis is an indication of this time factor, increasing with the age of the tumour. Within each grade the metastatic ratio is higher and the 5 year and 10 year survival less with the scirrhous than with the non-scirrhous tumours. The establishment of axillary metastases is closely connected with both the degree of malignancy and the time available, the unfavourable effect upon survival being greater in the scirrhous than in the non-scirrhous tumours.Another consequence of the passage of time, as indicated by fibrosis, is the gradual diminution of lymphoid infiltration (LI) which is mostly present in young tumours, especially those of high grades. The favourable effect of LI upon survival is demonstrated in the non-scirrhous tumours of grade III, possibly because of its great intensity, but this influence upon survival is lost as fibrosis increases and the intensity of the reaction diminishes.

Adenocarcinoma, Scirrhous↗

Altered expression of cyclins and cell cycle inhibitors in papillary thyroid cancer: prognostic implications.

Currently we lack biochemical or molecular markers that predict recurrence and metastases in thyroid cancer. Recent studies in a number of other human malignancies indicate that expression and/or subcellular localization of certain cell cycle regulators has prognostic utility. We have investigated the expression of cyclins D1 and E and of cyclin-dependent kinase inhibitor's p21 and p27 in papillary thyroid cancer (PTC) and correlated this with clinical/histological stage at diagnosis and with clinical outcome. PTCs were compared to normal thyroid, adenomas, and undifferentiated thyroid cancers (UTCs). Our studies indicate that PTCs and UTCs demonstrate low nuclear expression of cyclin E and p27, allowing a clear distinction between adenomas and these carcinomas (p < 0.004). A pattern of low nuclear expression of all four markers was observed in stage IV PTCs and UTCs, while stage I PTCs had low D1 and E accompanied by high p21 or p27. Expression of cytoplasmic cyclin D1 was significantly lower in stage IV PTCs and UTCs than in stage I-III PTC's (p </= 0.020), and appeared to correlate inversely with poor outcome in PTCs (p = 0.010). These studies suggest that evaluation of a panel of these markers and attention to their subcellular localization may be a useful adjunct in differentiating benign from malignant thyroid neoplasms and in predicting tumor behavior.

Adolescent↗