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Biomedical subjects

P Klemi

Publications and source records attributed to P Klemi.

At least 37 records · Page 2Linked to original sources

Association between syndecan-1 expression and clinical outcome in squamous cell carcinoma of the head and neck.

Syndecans are a family of cell-surface heparan sulphate proteoglycans which are involved in cell-matrix interactions and growth factor binding. Syndecan-1 binds basic fibroblast growth factor (bFGF) and several components of the extracellular matrix. Syndecan-1 expression is induced during keratinocyte differentiation and reduced during the formation of squamous cell carcinomas (SCCs). The purpose of this study was to examine the association of syndecan-1 expression with prognostic factors and clinical outcome in SCC of the head and neck. Frozen sections of 29 primary SCCs were analysed for syndecan-1 expression using immunohistochemical methods. Intermediate or strong staining for syndecan-1 was associated with a smaller primary tumour size (P = 0.0005) and higher histological grade of differentiation (P = 0.006) than negative or weakly positive staining. In a univariate analysis, syndecan-1-positive tumours were associated with higher overall (P = 0.001) and recurrence-free survival (P = 0.003) than those tumours with no or little syndecan-1 expression. The results suggest that syndecan-1 could be an important prognostic factor of SCC of the head and neck. Further studies on the prognostic significance of syndecan-1 expression in SCCs are warranted.

Adult↗

CT and ultra low field (0.02 T) MR imaging of uterine cervical carcinoma.

Nineteen pelvic MR and 21 CT examinations were performed in 21 patients with uterine cervical carcinoma. The results were compared with clinical (FIGO) staging in all patients, and with the histopathologic results after operation in 8. In the evaluation of local tumor growth CT agreed with clinical staging in 29%, MR imaging with clinical staging in 47% and CT with MR in 53%. The greatest discrepancy between the imaging methods and clinical examination was in the evaluation of parametrial extension. From 8 Stage I tumors with surgical confirmation the local tumor growth was overestimated with CT in 3 cases, with clinical examination in 2 and with MR imaging in 2 cases. CT and MR imaging at 0.02 T did not differ in the evaluation of parametrial tumor growth. Clinical examination overestimated parametrial growth but was relatively accurate in detecting vaginal wall involvement. MR imaging at 0.02 T is a convenient, inexpensive and accurate method for the local staging of early uterine cervical carcinoma.

Adenocarcinoma↗

Association of steroid hormone receptor content and flow cytometric DNA ploidy in endometrial carcinoma.

Flow cytometric DNA ploidy and sex steroid hormone receptor activity was measured in 55 endometrial carcinomas. DNA ploidy was measured on paraffin-embedded specimens and ER and PR activity was measured using both biochemical and immunohistochemical assay. Association of these parameters was tested using logistic regression model. Diploid or near diploid DNA histogram was seen in 40 cases (72.7%). All Grade 1 tumours (n = 15) were diploid whereas 38.5% of Grade 2 (n = 27) and Grade 3 (n = 13) tumours were aneuploid (grade 1 vs Grade 2 and 3, P = 0.0031). The mean value of ER was 109 +/- 120 (SD) fmol/mg protein for diploid tumours and 48 +/- 50 fmol/mg protein for aneuploid tumours (P = 0.0093). The corresponding values for PR were 226 +/- 262 fmol/mg protein and 75 +/- 102 fmol/mg protein (P = 0.0073), respectively. In immunohistochemical assay the mean HSCORE of ER was 45 +/- 77 for diploid tumours and 27 +/- 48 for aneuploid tumours (P = 0.43). The corresponding values for PR were 32 +/- 55 and 22 +/- 56, respectively (P = 0.58). In logistic regression analysis cytosolic PR content was associated with DNA ploidy.

Adult↗

Steroid hormone receptors and flow cytometric DNA ploidy in ovarian carcinoma.

The biochemical and immunohistochemical estrogen (ER) and progesterone receptor (PR) content and flow cytometric DNA ploidy was analyzed in five semimalignant and 35 malignant epithelial ovarian tumours. By biochemical assay, 67% of the tumours were ER-positive (> or = 5 fmol/mg protein) and 56% were PR-positive (> or = 10 fmol/mg protein). The corresponding values by immunohistochemical assay (with a HSCORE of 10 as the cutoff level) were 22% and 27%, respectively. DNA histogram measured from paraffin embedded specimens were diploid in 20% (7/35) and aneuploid in 80% (28/35) of the malignant tumours. All semimalignant tumours were diploid. The mean receptor values in the diploid and aneuploid tumours did not differ significantly and receptor-positive and receptor-negative tumours were evenly distributed in all stages and grades. In contrast, flow cytometric DNA ploidy was clearly associated with tumour stage (G2 = 10.52, Df = 3, P = 0.015) and histological differentiation (G2 = 20.57, Df = 3, P = 0.0001).

Adult↗

Disturbances of the endometrium in the luteal phase of cycles stimulated for in vitro fertilization and of normal cycles treated with vaginal progesterone.

Thirty-nine cycles of primarily (n = 32) and secondarily (n = 7) tubal infertile women were studied to evaluate the state of the luteal endometrium in women undergoing In Vitro Fertilization (IVF) without embryo transfer and in women in the normal unstimulated luteal phase with and without vaginal progesterone supplementation. One to four endometrial biopsies were performed in the luteal phase. Serum progesterone (P) and estradiol (E2) as well as the endometrial thickness were estimated on the same days. In groups stimulated for IVF, serum progesterone and estradiol levels were significantly higher (P < 0.01) compared to the control group. The endometrium was significantly thicker and grew more rapidly when cycles were stimulated, but the endometrial thickness did not correlate with endometrial maturation as assessed by histology. The endometrium was disturbed in a major part of the biopsies in all stimulated groups. Progesterone support had no beneficial effect. In women with unstimulated cycles, vaginal progesterone support caused mainly delayed gland maturation: the higher the dose of vaginal progesterone, the sooner the pathological changes in the endometrium were seen. With regard to endometrial histology, vaginal progesterone treatment in the luteal phase of IVF patients may not be advantageous.

Administration, Intravaginal↗

Neonatal benign sacrococcygeal teratoma may recur in adulthood and give rise to malignancy.

BACKGROUND: The capacity of neonatal sacrococcygeal teratomas (SCT) to recur is a well-recognized phenomenon. However, only a few studies have reported recurrence of the tumors beyond childhood. METHODS: A follow-up of patients for the detection of late recurrent SCT was performed in 45 patients, ages 4-43 years (mean, 21.5 years). All of the patients had been operated on in infancy for a benign SCT. RESULTS: Three adults with persistent or recurrent SCT were found. The recurrent tumors were diagnosed 21-43 years after the initial diagnosis and operative treatment. Two recurrences were histologically benign, and one was malignant. In the patient with the malignant recurrence, the coccyx was not removed primarily. The malignant recurrence was a mucinous adenocarcinoma and probably originated from a preexisting benign epithelial component of the teratoma. CONCLUSIONS: The capacity of a benign SCT to recur may be retained into adulthood. Follow-up of patients after operation for a SCT, even when the tumor is benign, should extend far beyond infancy. Abdominal radiographs may help detect late recurrent tumors with intrapelvic calcifications. When any recurrence is found, malignancy should be suspected.

Adenocarcinoma, Mucinous↗

Effect of DNA ploidy classification on prognosis in breast cancer.

A series of 327 breast cancers was analyzed for DNA ploidy by flow cytometry from paraffin-embedded tissue, and the resulting DNA histograms were classified independently by 6 researchers in the field as DNA diploid (Di), aneuploid (An), tetraploid (Te), multiploid (Mu), or technically uninterpretable. The frequency of diploid, aneuploid, tetraploid and multiploid cancers varied from 28 to 41%, 33 to 49%, 8 to 21% and 2 to 6%. According to the scale Di-An-Te-Mu, DNA ploidy was not significantly associated with breast-cancer mortality by 2 classifiers, but if DNA euploid cancers (Di+Te) were tested against non-euploid, or diploid cancers against non-diploid, all classifiers found DNA euploid and diploid cancers to have better prognosis. Mortality associated with diploid or tetraploid cancers decreased with improving histogram quality and increasing uniformity of classification, whereas that associated with aneuploid cancers remained unaltered. Among the cases where all classifiers agreed on ploidy, tetraploid, diploid and aneuploid cancers were associated with 100%, 88% and 68% 5-year survival rates. In this sub-set the S-phase fraction and possibly DNA ploidy were independent prognostic factors, together with histological grade, axillary node status, and primary tumor size.

Breast Neoplasms↗

Isolation of two keratinocyte cell lines derived from HPV-positive dysplastic vaginal lesions.

Explant cultures were started from human papillomavirus (HPV)-infected genital lesions in order to isolate and propagate abnormally differentiating cells from squamous intraepithelial neoplasia. A medium with high calcium concentration was used to induce terminal differentiation of cells from surrounding normal epithelium. Two cell lines with extended life-spans were established. The UT-DEC-1 cell line was derived from an HPV-33-positive mild vaginal dysplasia (VAIN I). In cultured UT-DEC-1 cells, HPV 33 DNA was detected with Southern-blot hybridization and the polymerase chain reaction (PCR) technique. The restriction pattern of HPV 33 changed during early passages and flow cytometric analysis detected a decrease in chromosomal DNA content. HPV 33 RNA from the E6-E7 region could be amplified by PCR at late passage. UT-DEC-2 cell line was derived from an HPV-16-positive moderate vaginal dysplasia (VAIN II). HPV 16 DNA was also detected in cultured cells by the PCR technique. The senescence of normal keratinocytes and growth selection in favor of aneuploid cells was observed by flow cytometric analysis at subsequent passages. Karyotype analysis showed clonal chromosomal abnormalities in both cell lines. To date, UT-DEC-1 cells have undergone 40 and UT-DEC-2 cells 25 passages. This study shows that the isolation of HPV-infected dysplastic cells can be achieved by culturing the cells in a medium with high calcium concentration. The cell lines presented provide the opportunity of evaluating the early stages of squamous-cell carcinogenesis.

Adult↗

DNA flow cytometry, nuclear morphometry, mitotic indices and steroid receptors as independent prognostic factors in female breast cancer.

Clinical features, 8 histological variables, 7 nuclear morphometric variables, 2 mitotic indices, oestrogen-receptor (ER) and progesterone-receptor content (PR), DNA ploidy and S-phase fraction (SPF) were entered in a Cox's model to assess their independent predictive value in 216 breast-cancer patients followed up for over 9 years. In the whole series, histological type (p = 0.007), volume-corrected mitotic index (M/V index) (p = 0.01), axillary-lymph-node (pN) status (p = 0.024) and the year of treatment (p = 0.045) predicted independently the recurrence-free survival (RFS). In a sub-analysis including SPF (n = 148), the year of treatment (p = 0.003), tumour diameter (p = 0.004), SPF (p = 0.022) and nuclear pleomorphism (p = 0.056) independently predicted the RFS. In a Cox's analysis of the whole series, tumour diameter (p less than 0.001), pN status (p = 0.001), PR status (p = 0.002) and the year of treatment (p = 0.021) were independent predictors of survival. In a separate analysis including also SPF (n = 148), tumour diameter (p less than 0.001), SPF (p = 0.003), pN status (p = 0.008) and the year of treatment (p = 0.015) proved to be independent prognostic factors. The results show that tumour diameter, pN status, M/V-index, histological type, SPF and PR status comprise a sufficient combination of prognostic factors in female breast cancer. In pN patients, age and SDPE may be of additional prognostic significance. The prognostic scores combining the independent prognostic variables reflecting both the proliferative rate and metastatic potential of the tumours are accurate predictors of the RFS and overall survival.

Adult↗

UT-MUC-1, a new mucoepidermoid carcinoma cell line, and its radiosensitivity.

Mucoepidermoid carcinoma is a fairly common malignant disease of the salivary glands. It is usually composed of two cell types, mucus-producing mucous cells and cells that have squamous differentiation with or without keratinization. The treatment of choice is considered to be radical surgical removal of the tumor. Radiotherapy has been recommended for high-grade or advanced tumors. Information on the radiosensitivity of mucoepidermoid cancer is scant, but based on clinical experience, the cancer appears to be only moderately radiosensitive. UT-MUC-1 is a newly established cell line from a poorly differentiated mucoepidermoid carcinoma. The cell line is diploid, but with complex karyotype abnormalities, giving a similar DNA index when measured with flow cytometry as that from the original tumor, and produces a tumor with characteristics typical for mucoepidermoid cancer when heterotransplanted to nude mice. The cell line is radiation resistant, with an area under the curve of 2.30 + 0.21 Gy when measured with a 96-well plate clonogenic assay. This correlates with the clinical outcome of the patient and the clinical experience of the radiosensitivity of this tumor type.

Aged↗

Magnetic resonance imaging of the uterus at an ultra low (0.02 T) magnetic field.

In vivo pelvic imaging of 39 women and in vitro relaxation time measurements of four uterine specimens were performed using an ultra low field (0.02 T) MRI unit. Average T1 times measured in vitro at 37 degrees C for the myometrium and endometrium were 206 ms (SD 47 ms) and 389 ms (SD 21 ms), respectively. Corresponding T2 times were 95 ms (SD 20 ms) and 167 ms (SD 13 ms). The proton relaxation of almost all myometrial specimens proved to be biexponential, but of all endometrial specimens was monoexponential. Contrast measurements between endometrium versus myometrium and myometrium versus the junctional zone were performed after imaging 18 volunteer women using different pulse sequence parameters. Normal uterine structures were optimally demonstrated by SE 700/70. Relatively short repetition times could be used, because spin-lattice relaxation times were short at the low magnetic field. Consequently, the short repetition times allowed averaging of four excitations to create adequate images within an acceptable scanning time. In addition to T2-weighted images a T1-weighted inversion recovery sequence with a short inversion time of 50 ms (IR 1000/50/40) adequately differentiated the three uterine zones. Although pathologic lesions of the uterus including leiomyomas, anomalies and carcinomas were well demonstrated, especially with the T2-weighted spin echo pulse sequence, further investigations are needed to evaluate the optimal technique for ultra low field MR imaging of uterine tumors.

Adenocarcinoma↗

Uptake of 2-fluoro-2-deoxy-D-[U-14C]-glucose during chemotherapy in murine Lewis lung tumor.

Mice bearing intramuscular Lewis lung tumor were treated with BCNU and doxorubicin (ADM) to study chemotherapy-induced changes in the uptake of 2-fluoro-2-deoxy-[U-14C]glucose (FDG). A decreased FDG uptake, tumor regression and a diminished proportion of aneuploid versus diploid cells as evaluated by DNA flow cytometry were seen after treatment with BCNU but not with ADM; HPLC indicated that most of the 14C activity in tumors was from FDG6-phosphate. The results suggest that changes in FDG uptake reflect the effectiveness of antitumor therapy. FDG may be valuable in follow-up studies of cancer treatment.

Adenosine Triphosphate↗

Significance of variation in DNA flow cytometric analyses from paraffin-embedded breast cancers. Evaluation of the grading efficiency of ploidy determination, DNA index, and S-phase fraction.

116 paraffin-embedded breast cancer samples were analyzed by flow cytometry. From each sample 3 consecutive 50 microns sections were cut for the study. The presence of neoplastic tissue was verified from light microscope sections cut before and after the adjacent sections. One laboratory started with one section from each block and was allowed extra sections when needed for analysis. At the end the laboratory obtained results from all 116 cases. The rest of the samples were studied by 2 other laboratories. Samples with results from 2 or 3 laboratories then allowed variability analysis and the estimation of the grading efficiency in a 2-grade system. Inconsistency in diploidy/aneuploidy distinction was present in 36 of 111 (32.4%) cases studied by two or three laboratories. This inconsistency was less obvious in samples graded as multiploid by at least one of the laboratories. The grading efficiency as analyzed from the results of 3 laboratories was 0.89, and of 2 laboratories, 0.84. The DNA index showed a slightly higher grading efficiency. At the cutoff point of 1.3, 91% of cases could be expected to be correctly classified into low ploidy and high ploidy groups (grading efficiency 0.91). The S-phase fraction had a mean grading efficiency of 0.89, a performance comparable to that of diploidy/aneuploidy distinction. In the light of the available data the flow cytometric analysis can add to the consistency of grading, especially when compared with subjective histological grading. However, the data do not suggest that flow cytometric analysis of paraffin sections as a grading method would be more consistent than quantitative histopathology from sections.

Aneuploidy↗

Risk factors for screen-detected breast cancer. A case-control study.

Risk factors for breast cancer (BC) detected in mammography screening were sought using a questionnaire among 31,927 women aged from 40 to 74 years who attended screening. Data from 204 women with screen-detected BC were compared with those of 612 controls who did not have BC in screening. Mothers of women with BC had more often BC than those of the controls (8% vs. 3%, odds ratio, OR, 3.18, 95% CI 1.59-6.35). Women with screen-detected BC were older at their first childbirth (25.7 years vs. 24.7 years, OR 1.61, 1.14-2.33), and younger at menarche (13.6 years vs. 13.8 years, OR 1.38, 1.00-1.91), but there was no significant difference in the body mass index, number of pregnancies, breast size, smoking, or in the use of contraceptive pills between the cases and the controls. In multivariate logistic regression analyses, late age at the first childbirth, BC in the mother, and early age at menarche were independent risk factors for screen-detected BC but they appear to be of limited value in targeting screening in the female population aged from 40 to 74 in order to improve its cost-effectiveness.

Adult↗

Nuclear morphometry and DNA flow cytometry as prognostic factors in female breast cancer.

OBJECTIVE: To evaluate the predictive value of traditional prognostic factors, nuclear morphometry, and flow cytometric data in invasive breast cancer. DESIGN: Open study. SETTING: One university hospital in Finland. SUBJECTS: 248 women with invasive breast cancer followed up for more than 11 years. MAIN OUTCOME MEASURES: Univariate and multivariate analysis of factors thought to indicate prognosis. RESULTS: Diameter of the tumour, lymph node status, S phase fraction. DNA index, the age of the patient, and the SD of nuclear perimeter were significant independent predictors in the whole series in a multivariate analysis. In node negative patients the SED of the nuclear perimeter and diameter of the tumour had independent prognostic value, whereas in node positive patients diameter of the tumour and the S phase fraction were independently related to survival. CONCLUSIONS: Diameter of the tumour is an important prognostic factor in breast carcinomas. Histoquantitative methods are superior to conventional histological techniques for the prediction of outcome in women with breast cancer.

Adult↗

Effects of radiation fractionation on four squamous cell carcinoma lines with dissimilar inherent radiation sensitivity.

The effect of radiation fractionation was investigated using a new 96-well-plate clonogenic assay in four squamous cell carcinoma lines. Earlier experiments had shown that two of the cell lines (UT-SCC-1A and UM-SCC-14A) were inherently relatively sensitive to irradiation, and two (UM-SCC-1 and UM-SCV-1A) relatively resistant. All of the four carcinomas from which the cell lines were established had poor clinical outcome. The radiation doses were given as a single exposure, or split into two or three equal fractions with a 24-h interval. The two inherently sensitive cell lines showed enhanced survival after radiation fractionation as compared with a single dose, whereas the resistant cell lines did not. The result suggests that both the inherent resistance of cancer cells to irradiation and the repair of sublethal radiation damage may lead to treatment failure, and that shortening of the total irradiation time may overcome cancer cell recovery between fractions in some, but not in all carcinomas.

Carcinoma, Squamous Cell↗

Lymphocyte homing and clinical behavior of non-Hodgkin's lymphoma.

Lymphocyte homing receptors (HRs) defined by Hermes antibodies (anti-CD44) and lymphocyte function associated antigen-1 (LFA-1, CD11a/CD18) are involved in lymphocyte binding to endothelial cells of high endothelial venules (HEVs) at sites where lymphocytes exit the blood. Their expression was correlated to the clinical behavior of 245 non-Hodgkin's lymphomas followed up for the median of 87 mo after the diagnosis. Lymphomas that showed no or weak staining intensity for HRs were more often of stage I (P = 0.005), disseminated less frequently hematogenously (P = 0.003), and had more favorable prognosis than lymphomas with intensive staining for HRs (P less than 0.0001) despite that they were more often histologically of high grade malignancy (P = 0.002). Expression of LFA-1 beta chain (CD18) did not correlate significantly with stage or survival, but had prognostic value in a subgroup of HR expression negative lymphomas (P = 0.03). HR staining intensity was an independent prognostic factor in a multivariate analysis. These findings indicate that Hermes/CD44 molecule is associated to the determination of the metastatic potential and prognosis of non-Hodgkin's lymphomas. They also reveal a new entity among non-Hodgkin's lymphomas, because lymphomas that express low levels of HR have favorable prognosis despite their often highly malignant histological appearance.

Adolescent↗