Search PubMed⌕ Search

Biomedical subjects

Robin T Vollmer

Publications and source records attributed to Robin T Vollmer.

At least 37 records · Page 2Linked to original sources
PubMed2004

COX-2, MMP-9, and Noguchi classification provide additional prognostic information about adenocarcinoma of the lung. A study of 117 patients from Brazil.

We report immunohistochemical staining results for cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in primary tumors of 117 patients with resected adenocarcinoma of the lung (median follow-up, 20 months). For COX-2, we graded the degree of tumor staining according to the sum of staining intensity and the proportion of cells staining. For MMP-9, we used morphometry to quantify cytoplasmic staining. We used the Cox proportional hazards model to analyze overall survival. With only 29 patients censored at last follow-up, after controlling for the effect of pathologic stage, staining for COX-2 and MMP-9 and subtype of tumor were related significantly to survival (P < 6 x 10(-5)). The effects of COX-2 and MMP-9 were opposite. Whereas any staining for COX-2 decreased the hazard and increased survival time, increased staining for MMP-9 increased the hazard and decreased survival time. The results also suggested that staining for COX-2 decreases with dedifferentiation. Our results suggest that staining for the combination of COX-2 and MMP-9 and categorizing tumors into papillary and nonpapillary types may provide important prognostic information for patients with resected adenocarcinoma of the lung; it is possible that these 3 variables could aid decisions about postoperative adjuvant treatment.

Adenocarcinoma↗
PubMed2004

Race and the linkage between serum prostate-specific antigen and prostate cancer: a study of American veterans.

Many aspects of prostate cancer differ between black men and white men, including incidence, stage, grade, sensitivities and specificities of serum prostate-specific antigen (PSA) levels, and survival. In general, the level of serum PSA reflects the mass of the prostate and the amount of tumor present, but the question to consider is whether this relationship is the same for blacks as for whites. If it is the same, then the ways we use serum PSA to screen, stage, and follow up white men with cancer should work equally for black men. If it is not, then we need alternative strategies for using serum PSA levels in blacks. I used regression analysis to study how the serum PSA level depends on prostate mass and the amount of tumor in 194 American veterans, including 87 black men. I found that black men produced higher levels of serum PSA for any given amount of tumor compared with whites, and I demonstrated that this difference can significantly affect the assessment of risk for outcomes in blacks.

Aged↗
PubMed2003

Immunohistochemical detection of occult lymph node metastases in non-small cell lung cancer: anatomical pathology results from Cancer and Leukemia Group B Trial 9761.

PURPOSE: Our purpose was to study the detection of occult metastases (OM) in regional lymph nodes using immunohistochemical stain for cytokeratin, and for this study we targeted clinical stage I patients with non-small cell lung cancer. EXPERIMENTAL DESIGN: The study comprised the first 193 patients entered onto Cancer and Leukemia Group B protocol 9761. All had clinically staged T(1-2)N(0)M(0) non-small cell lung cancer, and all underwent curative resections of their primary tumors. Samples of the primary tumor and lymph nodes were taken from lymph node stations 2-12 and shipped to a central laboratory, where each lymph node was histologically processed and stained with H&E as well as with immunohistochemical stain using antibodies to cytokeratin (AE1/3). RESULTS: Altogether, we examined 825 lymph nodes. Whereas routine H&E staining allowed us to detect 18 positive lymph nodes, immunohistochemical staining allowed us to detect 45 positive lymph nodes (P < 0.0001). There were 28 OM [i.e., those detectable only by immunohistochemistry (IHC)], and there was 1 metastasis detected only by H&E staining. The OM included 9 OM in N1 stations and 19 OM in N2 stations. Twelve patients with OM had skip metastases. Routine H&E staining upstaged six patients to N1, and IHC added another five. Routine H&E upstaged 9 patients to N2, and IHC added another 11. We also uncovered new details about the way in which H&E detection depends on metastatic tumor burden. Specifically, for the probability of detecting metastases by H&E to exceed 0.50, the maximum diameter of the metastasis must be greater than 0.23 mm. CONCLUSIONS: IHC detects greater than twice as many positive regional lymph nodes as does H&E staining, and the foci of tumor it detects are significantly smaller than those detected by H&E staining.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Morphometric evaluation of tumor matrix metalloproteinase 9 predicts survival after surgical resection of adenocarcinoma of the lung.

PURPOSE: Recently, several matrix metalloproteinases (MMPs) have shown promise as prognosticators in non-small cell lung cancer. In this study, we sought to validate the importance of MMP-9 and to study the relationships between MMP-9 and several other tumor or stromal markers. EXPERIMENTAL DESIGN: We examined MMP-9 and several other markers in tumor tissues from 152 patients with surgically excised adenocarcinomas of the lung. Their preoperative clinical stages were T(1-4)N(0)M(0); however, pathological exam of their resected tissues demonstrated that 33 were stage II, and 64 were stage III. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for MMP-9, and the outcome for our study was survival time until death from recurrent lung cancer. RESULTS: Multivariate Cox model analysis demonstrated that pathological stage was significantly related to survival time (P < 0.01), but quantitative staining of the tumor for MMP-9 added prognostic information (P < 3.0 x10(-16)) and was more strongly prognostic than pathological stage. In the subset of pathological stage I patients, staining for MMP-9 was also significantly associated with survival (P < 1.0 x10(-6)), and a cutpoint at the median staining of 11.2% for MMP-9 divided them into two groups with distinctive survival times. Those with MMP-9 > 11.2% had a median survival time of just 11 months. Those with MMP-9 < 11.2% had not reached a median survival and had a mean survival time of >62 months. CONCLUSIONS: Tumor staining for MMP-9 in resected adenocarcinoma of the lung is strongly related to survival. Patients with >11.2% staining in their tumors comprise a subset with a high hazard for dying of lung cancer and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.

Adenocarcinoma↗
PubMed2003

M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis.

BACKGROUND: The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis. METHODS: M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months. RESULTS: M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity. CONCLUSIONS: This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy.

Adult↗
PubMed2003

Multiple measures of carcinoma extent versus perineural invasion in prostate needle biopsy tissue in prediction of pathologic stage in a screening population.

The capacity of perineural invasion by carcinoma in prostate needle biopsy tissue to independently predict pathologic stage in radical prostatectomy tissues remains uncertain. We sought to determine, in a prostate specific antigen-based screening population, the ability of needle biopsy histologic grade, tumor extent, and perineural invasion to independently predict pathologic stage and margin status in the whole prostate gland. Perineural invasion, Gleason grade, percentage Gleason pattern 4/5 carcinoma, and multiple measures of needle biopsy tumor extent, including number of positive cores, percentage of positive cores, total percentage of carcinoma, greatest percentage of carcinoma in a single core, and total carcinoma length in millimeters, were captured for 215 men from a prostate specific antigen-based screening program diagnosed with prostate cancer in a median of six procured needle biopsy cores. Pathologic stage and surgical margin status were evaluated in corresponding completely embedded radical prostatectomy specimens. A logistic regression model was used to relate the endpoints of extraprostatic extension by carcinoma and/or positive margins to needle biopsy tissue findings. In univariate analyses, total percentage of carcinoma (p = 0.003), greatest percentage of carcinoma in a single core (p = 0.004), total tumor length in millimeters (p = 0.009), and fraction of positive cores (p = 0.02) were all significantly associated with extraprostatic (pT3) carcinoma, whereas all five measures of carcinoma extent in needle biopsy tissue were related to positive margins. Correlation coefficient determinations showed that all five measures of needle biopsy carcinoma extent were highly interrelated. In multivariate analyses, total percentage of carcinoma was significantly related to pathologic T stage (p = 0.003) and positive margins (p = 0.0002). In a multivariate model with the radical prostatectomy whole gland endpoint of either pT3 disease or positive margins, fraction of positive cores (p = 0.00001) was the only variable with significant predictive value. Perineural invasion by carcinoma in needle biopsy tissue was detected in 11% of cases. Neither presence nor absence of perineural carcinoma nor number nor percentage of positive nerves related to pathologic stage in univariate or multivariate analyses. Amount of carcinoma in prostate needle biopsy tissue, using multiple measurements but not perineural invasion, is a significant histologic attribute predictive of pathologic stage and margin status for men with prostate specific antigen screening detected prostatic carcinoma. Reporting of several measures of carcinoma extent in needle biopsy tissue is recommended.

Adult↗
PubMed2003

Basal cell hyperplasia in the peripheral zone of the prostate.

Basal cell hyperplasia in the prostate is often viewed as a transition zone proliferation, related to usual, nodular glandular, and stromal hyperplasia. Basal cell hyperplasia in the prostatic peripheral zone, the most common site for development of prostatic intraepithelial neoplasia and carcinoma, has not been previously characterized. We characterized the incidence and histomorphological attributes of basal cell hyperplasia in a series of 500 consecutive sextant needle core biopsy samples and in 26 completely embedded prostate glands from radical prostatectomy specimens. Comparative proliferation indices (by MIB-1 staining) and apoptotic indices (by TUNEL labeling) were quantitated for peripheral zone versus transition zone basal cell hyperplasia versus normal basal cells. The incidence of basal cell hyperplasia in prostate needle biopsy tissue was 10.2% (51 of 500 cases). Usual basal cell hyperplasia was detected in 8.2% of the 500 cases, and basal cell hyperplasia with prominent nucleoli, in 2.0% of cases. Basal cell hyperplasia in needle biopsy tissue was typically focal and associated with inflammation, which was usually lymphocytic, in 84% of cases. Peripheral zone basal cell hyperplasia was found in 23% of whole prostate glands. Peripheral zone basal cell hyperplasia was not observed to be in direct physical continuity with intraepithelial or invasive neoplasia. Peripheral zone and transition zone basal cell hyperplasia exhibited similar mean proliferation and apoptotic indices, at 1% and 0.07%, respectively. This proliferation index was elevated, and apoptotic index was decreased, relative to normal basal cells (P = 1 x 10(-7)). Basal cell hyperplasia in the peripheral zone is present in a significant minority of prostate needle biopsy samples and whole prostate glands. The presence of prominent nucleoli in basal cell hyperplasia may cause diagnostic concern for a neoplastic proliferation. The increase in cell number in basal cell hyperplasia appears to be due to a coordinate increase in proliferation index coupled with a diminished apoptotic index. The presence of inflammation in the majority of basal cell hyperplasia foci suggests that peripheral zone basal cell hyperplasia in untreated patients may represent a stereotyped response to injury such as that sustained because of inflammation.

Adult↗
PubMed2003

Tumor volume in prostate cancer and serum prostate-specific antigen. Analysis from a kinetic viewpoint.

Many have observed poor correlations between serum prostate-specific antigen (PSA) and tumor volume, and this noise undoubtedly reduces the diagnostic specificity of PSA. To explore this phenomenon, we addressed the problem from a theoretical viewpoint. Specifically, we used a compartmental model and first-order kinetics to develop the mathematics necessary to relate serum PSA to tumor volume. We found that the resulting model fit well the observed kinetic data of PSA measured after biopsy or prostatectomy. The model also predicted a linear relationship between PSA and the sum of volumes of benign and malignant tissues, but the coefficients for this linear equation are more complex than previously thought. They reflect not only how much PSA may be present in each tissue but also 3 rate parameters and the volume of serum. Much of the noise in the linkage between PSA and tumor volume is due to individual patient differences in the 3 rate parameters and in serum volume. Our model predicts that without ways to directly measure the several involved rate parameters, we will not be able to accurately predict tumor volume from PSA. Nevertheless, surrogates for the missing parameters may exist and could lead to statistical models that could improve the prediction of tumor volume.

Biomarkers, Tumor↗
PubMed2003

Serum CYFRA 21-1 in advanced stage non-small cell lung cancer: an early measure of response.

OBJECTIVES: Our objective was to test the prognostic importance of both the pretreatment level and change in serum CYFRA 21-1 after one cycle of chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to compare these two CYFRA variables to routine clinical stage and response as measured by imaging. PATIENTS AND METHODS: Our patients consisted of 58 with advanced NSCLC who were treated with chemotherapy. Fourteen were stage IIIa, 8 stage IIIb, and 36 stage IV, and none had received previous treatment. The choice of chemotherapy was left to the discretion of the treating physicians. We collected two serum samples, one before the first cycle of chemotherapy and the second before the second cycle, and analyzed these for serum CYFRA 21-1 using an electrochemiluminescence immunoassay and the ElecSys 2010 system (Roche Diagnostics Corp., Indianapolis, IN). We expressed changes in CYFRA in terms of the natural ratio logarithm of post-treatment to pretreatment CYFRA, and we used the Cox proportional hazards model to analyze survival time. RESULTS: Patients experienced an average drop of 27% in serum CYFRA after the first cycle of chemotherapy. Furthermore, the Cox model demonstrated that both the initial natural logarithm of serum CYFRA and presence of >27% drop in CYFRA were significantly related to subsequent survival (model P < 0.0006), but neither clinical stage nor clinical response related to survival (P > 0.1). CONCLUSION: In advanced stage NSCLC, the initial level of serum CYFRA appears to provide more prognostic information than clinical stage. Furthermore, a drop of >27% in CYFRA after one cycle of therapy adds prognostic information, so that this threshold appears to be an early measure of response to chemotherapy.

Adenocarcinoma↗
PubMed2002

The dynamics of prostate specific antigen during watchful waiting of prostate carcinoma: a study of 94 Japanese men.

BACKGROUND: For the moment, there is uncertainty about the usefulness of early treatment of localized prostate carcinoma, uncertainty about whether some patients with early cancer can be managed expectantly, and uncertainty about how such patients might be recognized. METHODS: The authors studied serial values of prostate specific antigen (PSA) in 94 Japanese men with diagnosed prostate carcinoma and who were managed by watchful waiting. Their median follow-up duration was 32 months (range, 1.6-118). The authors used a log-linear model to fit the values of PSA over time, and then they used the Cox survival model to relate the intercept (PSA amplitude) and slope (relative velocity) to observed local or systemic outcomes that were independent of PSA. RESULTS: The authors found that the log-linear model fit the serial values of PSA during watchful waiting very well. Prostate specific antigen amplitude related significantly to T classification (P = 0.0006), but not to grade (P > 0.2), and the relative velocity related significantly to both T classification (P = 0.009) and to grade (P = 0.02). Although the T classification, histologic grade, and log(PSA) at diagnosis were associated significantly with time to outcome, the combination of amplitude and relative velocity provided more information. These 2 PSA parameters resulted in a higher model likelihood ratio, and their individual P values in the Cox model were 0.0005 and 0.005, respectively. With these two in the Cox model, T classification, grade, log(PSA), and PSA doubling time provided no further significant information. CONCLUSIONS: A log-linear model seems to fit serial measurements of PSA during watchful waiting, and preliminary results suggest that both the amplitude and the relative velocity relate closely to clinical outcomes.

Aged↗
PubMed2002

Practical application of molecular genetic testing as an aid to the surgical pathologic diagnosis of sarcomas: a prospective study.

The strong correlation of specific reciprocal translocations with individual tumor types and the demonstration that polymerase chain reaction (PCR)-based methods can detect translocations in tissue samples have stimulated interest in the role of molecular genetic testing in diagnostic surgical pathology. To evaluate the clinical utility of PCR-based molecular analysis of soft tissue neoplasms in routine surgical pathology, 131 consecutive soft tissue tumors submitted for molecular genetic testing at a tertiary care teaching hospital were prospectively analyzed over a 36-month period. RT-PCR was used to test tumor RNA for fusion transcripts characteristic of malignant round cell tumors (including Ewing sarcoma/primitive neuroectodermal tumor, desmoplastic small round cell tumor, and alveolar rhabdomyosarcoma), spindle cell tumors (including synovial sarcoma and congenital fibrosarcoma), and fatty tumors (myxoid liposarcoma). DNA sequence analysis was used to confirm the identity of all PCR products, and the PCR results were compared with the histopathologic diagnosis. We found that sufficient RNA for RT-PCR-based testing was recovered from 96% of the 131 cases and the percentage of tumors that tested positive for the associated characteristic fusion transcript was in general agreement with those reported in the literature. DNA sequence analysis of PCR products identified both variant transcripts and spurious PCR products, underscoring the value of product confirmation steps when testing formalin-fixed, paraffin-embedded tissue. Only in rare cases did testing yield a genetic result that was discordant with the histopathologic diagnosis. We conclude that PCR-based testing is a useful adjunct for the diagnosis of malignant small round cell tumors, spindle cell tumors, and other miscellaneous neoplasms in routine surgical pathology practice.

Base Sequence↗
PubMed2002

Carcinoma extent in prostate needle biopsy tissue in the prediction of whole gland tumor volume in a screening population.

Increasing prostate tumor volume has been shown to correlate with numerous adverse prognostic indicators for patients with prostate carcinoma The ability to predict tumor volume from pretreatment parameters is potentially critical in the stratification of patients for different management strategies. We assessed the capacity of preoperative variables to predict tumor volume in 100 men diagnosed with prostate cancer in a prostate-specific antigen (PSA)-based screening program. Preoperative information included total serum PSA concentration and needle biopsy tissue variables, including Gleason score, number of positive cores, linear extent of carcinoma in millimeters, greatest percentage of carcinoma (in a single core), total percentage of carcinoma (all cores), presence of perineural invasion, and percentage of high-grade carcinoma. The postoperative end point was total tumor volume in radical prostatectomy tissue, calculated by image analysis. We determined independently significant factors and generated a predictive modelfor whole gland tumor volume. Total tumor volume was related significantly in multivariate analysis to 3 preoperative variables: linear extent of carcinoma, exponential number of positive cores, and serum PSA. A predictive model generated based on these 3 variables accounted for only 65% of the natural deviance of the data owing to data-point scatter for individual patients, suggesting that additional variables are needed to more accurately predict tumor volume. Findings highlight the importance of reporting quantitative measures of tumor amount in prostate needle biopsy specimens; several measures of tumor extent (vs 1 measure) provide maximal information on prostate cancer size.

Adenocarcinoma↗
PubMed2002

Diffusion-weighted imaging in a patient with vertebral and epidural abscesses.

In this report, we describe the appearance of the spinal vertebral body and epidural abscesses in a patient who underwent diffusion-weighted imaging of the spine and CT-guided aspiration of one of the abscesses. The abscesses were hyperintense relative to the surrounding tissues on diffusion-weighted images, and they appeared dark on apparent diffusion coefficient maps; these findings were consistent with those of published reports of the brain and liver.

Aged↗