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PubMed1992

Differences in the integration pattern and episomal forms of human papillomavirus type 16 DNA found within an invasive cervical neoplasm and its metastasis.

Human papillomavirus (HPV) type 16 DNA was found in three separate neoplastic lesions within a female patient. The physical state of the viral DNA in each lesion was determined by two-dimensional agarose gel electrophoresis. The primary cervical tumor contained large amounts of several distinct episomal forms as well as integrated HPV DNA. Metastatic tumor tissue found in the vagina had greatly reduced levels of episomal DNA and a viral DNA integration pattern that was different from that of the primary tumor. The vulvar carcinoma in situ had what appears to be free and integrated forms of viral DNA. The results show that although metastatic tissue retained HPV DNA, further rearrangements of the integrated viral DNA pattern found in the primary tumor may occur with a dramatic decrease of episomal forms during malignant progression.

Carcinoma, Squamous Cell↗

PubMed1980

Ultrasound patterns of disorders affecting the gastrointestinal tract.

A mass associated with the gastrointestinal tract was detected by sonography in 33 patients. Etiologies included primary or metastatic tumor; intussusception; inflammation secondary to bowel infarction, pancreatitis, or irradiation; and a dilated, fluid-filled gut related to retained gastric contents, obstruction, ileus, or an ileal bypass. Mesenteric or omental changes were identified with inflammation and frequently with metastatic disease. The diagnosis was confirmed by repeat sonography, abdominal radiography, barium examination of the small bowel, computed tomography, surgery, or autopsy. Ultrasound patterns are characteristic in tumor, intussusception, and inflammation; specific features allowing differentiation between tumor and inflammation are described. Colonic haustra, valvulae conniventes, or bowel contours and peristalsis on real-time sonography are helpful in identifying fluid-filled bowel loops.

Adult↗

PubMed2006

Mucin profiles in signet-ring cell carcinoma.

CONTEXT: Signet-ring cell carcinoma (SRCC) is a poorly differentiated mucin-producing adenocarcinoma that may arise from many different organs, but all SRCCs share identical morphology. It is not possible to differentiate sites of origin for metastatic SRCC based on morphology alone. Mucins are high-molecular-weight glycoproteins differentially expressed in glandular epithelia and in adenocarcinomas. OBJECTIVE: To identify mucin profiles of primary and metastatic SRCCs using immunohistochemistry to determine whether mucin staining could help distinguish sites of origin. DESIGN: Forty-seven SRCCs, including 38 primary (21 stomach, 11 colorectum, and 6 breast) and 9 metastases from these primary sites were retrieved from archival files. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC (MUC5), and MUC6 on separate slides. Cytoplasmic staining was scored based on proportion of positive tumor cells as follows: 0+ (<5%), 1+ (5%-25%), 2+ (26%-50%), and 3+ (>50%). Mucin profiles were recorded as MUC+, MUCv, and MUC- for consistent, variable, and negative expression, respectively. RESULTS: The mucin profiles for gastric, colorectum, and breast SRCCs are MUC1.2.4.5.6v, MUC2.4+/MUC5v/ MUC1.6-, and MUC1+/MUC2.5.6v/MUC4-, respectively. Mucin profiles of metastatic cases shared profiles with their respective primaries. CONCLUSIONS: Signet-ring cell carcinomas of the stomach, colorectum, and breast have distinct mucin expression patterns that are maintained in metastases. Mucin profiling may be useful to identify the origin of a metastatic SRCC of unknown primary.

Carcinoma, Signet Ring Cell↗

PubMed1999

Genetic pattern of prostate cancer progression.

Genetic alterations in primary prostate cancer (CaP) have been extensively studied, yet little is known about the genetic mechanisms underlying progression of primary CaP to metastatic prostate cancer. As a result, it is not possible to distinguish clinically indolent localized disease from potentially life-threatening tumors with high metastatic potential. To address this question, we collected tissue from 34 autopsy-derived metastases, samples rarely analyzed in previous studies. These were compared to a separate set of 17 prostatectomy specimens containing 22 foci of CaP associated with 49 examples of high-grade prostatic intraepithelial neoplasia (PIN), a histological precursor of CaP. We compared the loss of heterozygosity (LOH) profiles of high-grade PIN, primary CaP and metastases by analyzing 33 microsatellite markers previously found to have high frequencies of LOH in primary CaP. These markers were on chromosomes 5q, 6q, 7q, 8p, 9p, 10q, 11p, 13q, 16q, 17, 18q and 21q. In addition, markers on chromosomes 4p, 11q, 14q and 20q with no reported LOH in primary CaP were analyzed to determine the frequency of background LOH. In PIN lesions, the rate of LOH was significant only at D5S806 (20%) and D16S422 (29%). In addition, different PIN lesions within the same prostate gland were genetically diverse, indicating divergent evolution of synchronous neoplastic precursor lesions. LOH frequency was progressively higher in primary CaP and metastatic lesions. In primary CaP, significant losses occurred at the 8p, 10q, 11p, 16q, 17p, 18q and 21q loci (range 17-43%). Distinct patterns of LOH frequencies were observed in primary CaP compared with metastases. Although some loci (D16S422, D17S960, D21S156) showed similar frequencies of LOH in primary CaP and metastatic CaP, most other loci showed up to 7-fold metastasis-related increases. The metastatic samples revealed previously unrecognized prostate cancer LOH at D5S806, D6S262, D9S157, D13S133 and D13S227. These significant stage-specific differences in LOH frequency specify genetic loci that may play key roles in CaP progression and could represent clinically useful biomarkers for CaP aggressiveness.

Adenocarcinoma↗

PubMed2005

Ultrasonography using simple diagnostic criteria vs palpation for the detection of regional lymph node metastases of melanoma.

OBJECTIVES: Our aims were (1) to compare the respective ability of ultrasonography and palpation to detect nodal metastasis during initial staging and follow-up in patients having melanomas and (2) to assess, we believe for the first time, which ultrasound criteria should be used to define metastasis in cases of cutaneous or mucosal melanoma. DESIGN: Prospective single-center study. Nodal metastasis was confirmed by histopathologic evaluation. SETTING: Dermatology and radiology departments of a university hospital. PATIENTS: A total of 160 new consecutive patients with stage I to stage III melanoma. INTERVENTION: Experienced operators independently performed 391 paired palpation and ultrasonographic examinations. MAIN OUTCOME MEASURES: Firm enlarged nodes found on palpation were considered metastatic. On ultrasonographic examination, circular or oval hypoechoic lymph nodes lacking hyperechoic hila were considered metastatic (stringent criteria). Nodes with 2 or fewer of these patterns and other published signs of metastasis (ie, intranodal nodular hypoechoic focus and irregularity of the node margin) were considered suspicious. RESULTS: Over the 6-year study period 33 patients developed nodal metastasis. For palpation and ultrasonography using the stringent criteria, respectively, sensitivity was 41.5% (95% confidence interval [95% CI], 29.6-53.5) and 76.9% (95% CI, 66.7%-87.2%) (P<.001) and specificity was 95.7% (95% CI, 93.5%-97.9%) and 98.4% (95% CI, 97.1%-99.8%) (P<.05). Including ultrasonographically suspicious lymph nodes significantly lowered specificity (86.2% [95% CI, 82.5-89.9]) (P<.05) without improving sensitivity. Previous lymphadenectomy had little impact on ultrasonographic findings. CONCLUSION: Ultrasonography using stringent criteria of nodal metastasis, which are easy to identify and reliable, is superior to palpation for early detection of regional lymph node metastases of melanoma.

Adult↗

PubMed1989

Prognostic significance of the DNA content of renal carcinoma.

DNA analysis was performed on fresh frozen samples of the primary tumor in 32 patients with renal carcinoma (13 with apparently localized disease and 19 with metastases at presentation). A comparison of ploidy with staging and standard histologic variables was performed. None of the patients who presented without metastases died of disease during the follow-up period. Eleven of 13 patients of this group had a diploid/near diploid pattern, and metastases developed in only one patient. Patients with metastatic disease and a diploid/near diploid DNA content had a significantly better survival rate than those with aneuploid primary tumors. Statistical analysis showed that grade and ploidy contributed significant but independent prognostic information. We concluded that DNA content is a useful prognostic factor in renal carcinoma.

Adult↗

PubMed2005

Differential expression of insulin-like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia: combined cDNA suppression subtractive hybridization and microarray study.

BACKGROUND: Hydatidiform mole (HM), the most common type of gestational trophoblastic diseases, can be considered as placenta with abnormal chromosome composition with potential of malignant transformation. Few biologic markers can predict subsequent development of persistent gestational trophoblastic neoplasia (GTN) requiring chemotherapy. METHODS: Suppression subtractive hybridization (SSH) combined with cDNA microarray was used to compare the differential expression pattern of HM that spontaneously regressed and that subsequently developed metastatic GTN. Tissue-specific chips were constructed from the subtracted cDNA libraries, followed by cDNA microarray analysis. Verification by quantitative RNA analysis by real-time polymerase chain reaction (PCR) and immunohistochemical analysis was performed in 23 genotyped complete HM. RESULTS: Sixteen differentially expressed transcripts were identified. Quantitative RNA analysis confirmed down-regulation of ferritin light polypeptide (FTL) (P = 0.037) and insulin-like growth factor binding protein 1 (IGFBP1) (P = 0.037) in HM that subsequently developed GTN when compared with those HM that regressed. Immunohistochemical analysis further confirmed reduced IGFBP1 protein (P = 0.03) expression in HM that developed GTN. CONCLUSIONS: Findings showed that reduced expression of genes related to cell invasion and immunosuppression, especially FTL and IGFBP1, were associated with development of GTN, and this finding may provide a better understanding of the pathogenesis of GTN. The potential application of FTL and IGFBP1 in management of patients with HM should be explored.

Adolescent↗

PubMed1987

Nonosseous sarcomas in a military hospital.

This is a retrospective review of 67 patients with soft tissue or visceral sarcomas treated during 1973-1982. There were 40 males and 27 females. The mean age was 36 with a range of 1 to 77 years of age. The most common histologic subtypes were rhabdomyosarcoma (19%), malignant fibrohistiocytoma (13%), fibrosarcoma, leiomyosarcoma, dermatofibrosarcoma protuberans (12% each), and liposarcoma (10%). Among the 42 soft tissue sarcomas 33% occurred in the trunk, 35% and 21% in the lower and upper extremities, and 10% in the head and neck region. Among the 25 visceral sarcomas, 16% were in the thorax, 56% involved abdominal or retroperitoneal organs, and 28% were in the head and neck region. Overall, 33 of the 54 patients with early sarcomas were treated by surgical resection alone while 21 others had postoperative adjuvant radiotherapy and/or chemotherapy. Factors influencing survival are presented and patterns of metastasis discussed. Overall, 45% of the patients showed metastatic disease either at diagnosis (15%) or during the follow-up period (30%). The lung was involved in two-thirds of the cases and was the most common site of spread. In patients with rhabdomyosarcoma and malignant fibrohistiocytoma, regional lymph node metastasis was noted in 36% and 17%, respectively.

Adolescent↗

PubMed2002

Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression.

OBJECTIVE: Impairment of cell adhesion plays a vital role in tumor progression. E- and N-cadherin, CD9, and KAI1 are all adhesion molecules that have been implicated in the progression of several different tumor types. To help explain the potential role these adhesion molecules have in ovarian cancer, comparisons were made between expression patterns in normal ovary and various grades of primary and metastatic epithelial ovarian cancers. METHODS: Thirty-two primary and 8 metastatic human ovarian epithelial carcinomas and 18 samples of normal ovarian tissue were examined for adhesion molecule expression using immunohistochemistry. RESULTS: KAI1 and CD9 revealed an inverse relationship between tumor grade and expression levels, characterized by high expression in low-grade tumors and low expression in high-grade tumors and metastases. KAI1 and CD9 also demonstrated a shift in cellular localization from the membrane in grade 1 tumors to the cytoplasm in grade 3 tumors. N-cadherin expression showed a positive trend between expression levels and tumor grade. E-cadherin expression varied little between different tumor grades and metastases. Inclusion cysts (n = 6) and surface invaginations often strongly expressed KAI1, CD9, and E-cadherin. KAI1 expression was variable in ovarian follicles and corpora lutea depending on their stage of development. CONCLUSIONS: Although sample size is limited, these findings suggest that progression of ovarian epithelial carcinomas is associated with down-regulation and altered cellular localization of KAI1 and CD9. In addition, variable KAI1 expression during follicular and luteal development suggests that it has a physiological function in the ovary. Further investigation will be needed to see if it is also regulated this way during progression of ovarian cancers.

Antigens, CD↗

PubMed1976

Abdominal desmoid masses in Gardner's syndrome.

Abdominal masses, "desmoid tumors," occur in approximately 4% of patients with Gardner's Syndrome, usually 1--3 years after total colectomy. Histologic sections usually resemble those of an infiltrating fibrous tumour, a desmoid lesion. The radiographic pattern may be similar to any diffuse abdominal retroperitoneal tumor, metastatic disease, lymphoma, or possibly retractile mesenteritis. The clinical setting usually differentiates these entities.

Abdominal Neoplasms↗

PubMed1990

DNA ploidy pattern and amplification of ERBB and ERBB2 genes in human gastric carcinomas.

The DNA ploidy pattern and amplification of ERBB and ERBB2 genes were examined in paraffin-embedded tissue from gastric carcinomas using flow cytometry and a slot-blot hybridization technique. The incidence of aneuploidy in well differentiated adenocarcinomas (56%) was significantly higher (p less than 0.05) than that in poorly differentiated adenocarcinomas (21%). The DNA ploidy pattern was not remarkably different between the primary tumors and metastatic deposits in lymph nodes. Of the nine specimens having an aneuploid stem cell line in the primary tumor and/or in metastases, three showed ERBB2 gene amplification and one showed ERBB gene amplification. The incidence of epidermal growth factor (EGF) immunoreactivity in tumor cells showed no difference between diploid and aneuploid tumors. These findings indicate that aneuploidy is frequently associated with amplification of ERBB and ERBB2 genes.

DNA, Neoplasm↗

PubMed2001

[PET studies of recurrent rectal carcinoma. Fundamental aspects of lymphatic metastasis of visceral and somatic carcinomas].

We have shown previously that the bodies of vertebrates are made of a somatic and a visceral component, separated by thin fascial sheets (Chirurg 66: 1230). We postulated that advanced visceral cancers are confined in their pattern of lymphatic spread to one or a few distinct metastatic pathways. In this they are fundamentally different from somatic cancers. To investigate this hypothesis in vivo, we evaluated positive lymph nodes (LNs) on PET scan series of 58 consecutive patients with rectum cancers (RC) compared to breast cancers (BC). We conclude that in RC, a visceral cancer spreads mostly along only one caudocranial pathway (regional, para-aortic, mediastinal, supraclavicular LNs) and never affects somatic LNs. In contrast, BC and urogenital carcinomas, as somatic cancers spread to regional somatic LNs, but do not affect visceral LNs.

Breast Neoplasms↗

PubMed2001

[PET examinations of recurrent rectal carcinoma, 2].

Breast Neoplasms↗

PubMed1978

Hepatitis B and primary hepatocellular carcinoma in a European population.

The prevalence of serological markers of active of past hepatitis-B virus (H.B.V.) infection was determined in 80 Greek patients with primary hepatocellular carcinoma (P.H.C.), 160 age and sex matched controls and 40 patients with metastatic liver cancer (M.L.C.). The relative risk of the various patterns of H.B.V. serological markers for P.H.C. was calculated. Active H.B.V. infection, as indicated by positive tests for hepatitis-B surface antigen (HBsAg), or antibody to hepatitis-B core antigen (anti-HBc) without antibody to HBsAg) (anti-HBs), was associated with P.H.C. (relative risk 10.4) but not with M.L.C. (relative risk 1.2). Patients without markers and those who had recovered from hepatitis B (anti-HBs-positive) had approximately the same low risk for P.H.C. (relative risk 0.8). Active infection was more common in P.H.C. patients with co-existing cirrhosis than in those without cirrhosis (67% versus 26%). Thus the relationship between active hepatitis B and P.H.C. seen in African and Asian populations is now seen in a European Caucasian population with different racial, environmental, and dietary circumstances.

Adult↗

PubMed2002

Development of a large animal model for lung tumors.

PURPOSE: Minimally invasive locoregional therapies for human liver tumors have been developed in recent years, and similar treatment options may be successful in the management of human lung cancer. Our goal was to develop a lung tumor model in a large animal to simulate human lung cancer for preclinical assessment of novel therapeutic options. MATERIALS AND METHODS: Fresh canine transmissible venereal tumor (cTVT) fragments were inoculated into the lungs of 10 dogs by intraarterial (n = 2) or percutaneous (n = 8) methods. Cyclosporin was administered to produce immunosuppression in nine of the dogs. Tumor growth was monitored at regular intervals (every 1-2 weeks) by computed tomography. All animals were killed between 6 and 10 weeks after inoculation; complete necropsy examinations were performed and appropriate tissues were removed for gross and histopathologic evaluation. RESULTS: Administration of tumor fragments into the right apical pulmonary artery resulted in the development of more than 20 well-defined scattered pulmonary nodules in the affected lung segment. Nodules grew to a maximum diameter of 12 mm in 10 weeks. Percutaneous inoculation of tumor fragments resulted in more predictable growth of solitary tumors (range, 7-35 mm in diameter) in the transplantation bed. No tumor growth was observed in the dog that did not receive cyclosporin. CONCLUSIONS: Percutaneous inoculation and intraarterial transplantation of cTVT fragments in the canine lung result in predictable patterns of tumor growth resembling the solitary pulmonary nodules and metastatic disease found in humans. In addition, cyclosporin administration may be necessary to promote growth of viable tumor.

Animals↗

PubMed2003

Patterns of recurrence in patients with melanoma and histologically negative but RT-PCR-positive sentinel lymph nodes.

BACKGROUND: We studied the patterns of recurrence of patients with only reverse transcriptase-polymerase chain reaction (RT-PCR) evidence of regional nodal spread to see whether or not proposed treatment interventions are likely to be effective. STUDY DESIGN: One hundred seventy-five patients who underwent selective lymphadenectomy for clinical stage I and II melanomas were included in this analysis. We preserved a portion of each sentinel lymph node (SLN) in liquid nitrogen in the operating room and performed RT-PCR on the specimens to detect the melanoma/melanocyte-specific marker tyrosinase. We then compared the pattern of recurrence (regional dermal metastases, regional nodal recurrence, or distant metastatic spread) of the patients with histologically positive SLNs to that of patients who had histologically negative SLNs. RESULTS: The mean followup time of the 175 patients was 33.83 months (SD = 15.94, median = 34.17, maximum = 62.95, minimum = 6.21). Thirty-four patients had at least one histologically positive SLN, and 17 of these patients had a recurrence (50%). Of the 141 patients that had histologically negative SLNs, 73 had SLNs that were also negative for tyrosinase by RT-PCR, and none of these patients had a recurrence. Of the 68 patients that had histologically negative but RT-PCR-positive SLNs, 14 had a recurrence (20.6%). CONCLUSIONS: Because the pattern of recurrence of patients with only RT-PCR evidence of melanoma in SLNs was identical to that in patients who had histologically evident melanoma in the SLN and underwent subsequent completion lymphadenectomy, we conclude that completion lymphadenectomy might be ineffective in decreasing the recurrence rate of patients with only RT-PCR evidence of melanoma in SLNs.

Biomarkers, Tumor↗

PubMed1982

Clinical kinetics of 1, 4-dihydroxy-5,8-bis [(2-[(2-hydroxyethyl) amino] ethyl] amino ]-9, 10-anthracenedione.

The clinical kinetics of 1, 4-dihydroxy-5,8-bis[[ 2-[(2-hydroxyethyl) amino] ethyl] amino]-9,10-anthracenedione dihydrochloride (DHAQ) are reported. DHAQ, 1 to 3 mg/m2, was administered as an intravenous bolus to six patients with metastatic cancer. Plasma clearance of the drug followed a biphasic pattern with a harmonic mean initial half-life (t 1/2) of 13.7 min and a terminal t 1/2 of 37.4 hr. Recovery of unchanged drug in the urine was 6.8% at 24 hr and 7.3% at 72 hr, while the corresponding recovery of total radioactivity was 9.4% and 11.3%. Apparent volume of distribution of DHAQ was about 13.8 +/- 2.9 l/kg. Total clearance was 238.7 ml/kg/hr, twice the creatinine clearance.

Adult↗

PubMed2003

Contrast media-enhanced power Doppler sonography for evaluation of hemangiomas and malignant tumors in the liver.

AIM: To evaluate the characterization of liver hemangiomas and malignant tumors using power Doppler sonography before and after intravenous injection of a sonocontrast agent. METHODS: Forty-five patients with 57 liver tumors (22 hemangiomas, 24 metastases, 10 hepatocellular carcinomas (HCC) and one cholangiocellular carcinoma) were examined prospectively. The distribution (peripheral, central, mosaic) and extent (none, minimal, moderate and strong) of intratumoral flow pattern in each sonographic examination was subjectively classified. RESULTS: The administration of the sonocontrast agent by bolus injection caused enhancement to gradually increase up to 2 min and lasted for 4-5 min. After injection of contrast agent, flow signals appeared or increased in 34 tumors. No signal enhancement was observed in 18 hemangiomas, four metastases and one HCC. The sensitivity and specificity of intratumoral vascularity for the detection of malignant liver tumors was 37.1 and 90.9% for unenhanced power Doppler sonography, and 85.7 and 81.8% for contrast-enhanced power Doppler sonography, respectively. CONCLUSION: Contrast-enhanced power Doppler sonography is superior to unenhanced power Doppler sonography in the demonstration of malignant tumor vascularity, and is helpful in differentiating between hemangiomas and malignant liver tumors. A specific flow pattern within the tumor is not established in primary and metastatic malignant tumors with contrast-enhanced power Doppler sonography.

Adult↗