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D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 55 records · Page 3Linked to original sources
PubMed2000

Extranodal extension in lymph node-positive prostate cancer.

Evaluation of extranodal tumor extension may provide prognostic information for patients with epithelial malignancies. However, its importance for the patient who has prostate cancer with regional lymph node metastasis requires further investigation and clarification. This study was performed to evaluate the prognostic significance of extranodal extension (ENE) in a large series of node-positive patients. The study group included 212 node-positive patients who were treated by bilateral pelvic lymphadenectomy, radical retropubic prostatectomy, and androgen deprivation between 1987 and 1992 at the Mayo Clinic. ENE was defined as cancer perforating through the lymph node capsule into perinodal tissue. Nodal cancer volume was measured by the grid method. Univariate and multivariate risk ratios (RR) for distant metastasis-free and cancer-specific survival were estimated using the Cox proportional model. The mean follow-up was 6.3 years (median, 6.1 years). Distant metastasis-free and cancer-specific survival at 5 years for all patients was 91% and 95%, respectively. ENE was found in 126 of 212 patients (59%). The presence of ENE was not significantly associated with distant metastasis-free (RR = 1.6; 95% confidence interval [CI], 0.7 to 3.9) or cancer-specific survival (RR = 2.2; 95% CI, 0.7 to 6.8). Among 98 patients with a single positive node, there was no significant difference in distant metastasis or cancer-specific survival according to the presence of ENE (P = .88 and P = .36, respectively). After adjusting for Gleason score, DNA ploidy, and ENE, only nodal cancer volume was significantly associated with adverse distant metastasis-free (RR = 1.9; 95% CI, 1.5 to 2.8) and cancer-specific survival (RR = 1.4; 95% CI, 1.1 to 1.9). Our data indicate that the presence of ENE is not associated with unfavorable survival in patients with node-positive prostate cancer treated by radical retropubic prostatectomy, bilateral pelvic lymphadenectomy, and androgen deprivation therapy. In contrast, nodal cancer volume was predictive of distant metastasis-free survival and cancer-specific survival.

Adenocarcinoma↗
PubMed2000

10q23.3 loss of heterozygosity is higher in lymph node-positive (pT2-3,N+) versus lymph node-negative (pT2-3,N0) prostate cancer.

Loss of heterozygosity (LOH) in the region of 10q23.3 has been associated with multiple tumors, including glioblastoma multiforme, melanoma, endometrial carcinoma, and prostate carcinoma. The tumor suppressor gene, PTEN/MMAC1, is also located in this region, and, in addition to other tumor types (eg, glioblastoma multiforme, endometrial, and melanoma), PTEN/MMAC1 mutations have been found in prostate cancer cell lines, xenografts, and hormone refractory prostate cancer tissue specimens. The aim of this study was to evaluate LOH at 10q23.3 as a marker of cancer progression in node-positive prostate cancer. Genetic alterations in the region of 10q23.3 were assessed in 23 node-positive (pT2-3, N+) and 44 node-negative prostate (pT2-3, N0) cancers with D10S532, D10S1687, D10S541, and D10S583 flanking polymorphic genetic markers; PTENCA, a genetic marker within PTEN/MMAC1, was also tested. Using DNA from paired normal and microdissected tumor samples, LOH at microsatellite loci was determined after polymerase chain reaction amplification. LOH in at least 1 marker was identified in 14% (6 of 44) of lymph node-negative and 43% (10 of 23) of lymph node-positive prostate cancers (chi-square test, P = .007). This increase in genetic alterations in node-positive prostate cancer suggests that 10q23.3 is a marker for metastatic progression.

Adenocarcinoma↗
PubMed2000

Diagnosis of prostatic intraepithelial neoplasia: Prostate Working Group/consensus report.

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostatic carcinoma. PIN has a high predictive value as a marker for carcinoma, and its identification in biopsy specimens warrants repeat biopsy for concurrent or subsequent carcinoma. The only methods of detection are biopsy and transurethral resection; PIN does not significantly elevate serum PSA concentration or its derivatives, nor does it induce a palpable mass, and cannot be detected by ultrasound. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention. Radiation therapy is also associated with a decreased incidence of PIN.

Adenocarcinoma↗
PubMed2000

Epidemiology of high-grade prostatic intraepithelial neoplasia.

This review summarizes published data dealing with the prevalence of high-grade prostatic intraepithelial neoplasia (HGPIN) in a variety of prostate tissue samples. Additionally, we have attempted to document the relationship between HGPIN and the pathological parameters of prostate cancer in autopsy and radical prostatectomy specimens. Studies reporting the prevalence of HGPIN in needle biopsies, transurethral resection specimens and radical prostatectomy specimens, and those documenting the lesion in postmortem settings are compared. We also summarize studies in which the distribution and/or extent of HGPIN was correlated with prostate cancer stage, grade and volume. There is significant variation in the reported frequency of HGPIN, particularly in needle biopsy specimens, with a range of 0.8-23.9%. The factors responsible for these discrepancies include the population studied, the limited sample size that needle biopsies represent, diagnostic inconsistencies and, possibly, tissue preparation/staining variables. Because of the important implications a diagnosis of HGPIN carries, there is a pressing need to achieve greater consistency in diagnosing and reporting the lesion. Better targeted educational efforts, including teaching courses, websites with illustrations and the possibility of teleconsultations, are among possible means to attain this goal. Better documentation of the evolution of HGPIN to cancer through clinical follow-up is also recommended.

Biopsy, Needle↗
PubMed2000

Cellular and molecular pathology of prostate cancer precursors.

Prostate cancer is usually heterogeneous and multifocal, with diverse clinical and morphologic manifestations. Current understanding of the molecular basis for this heterogeneity is limited, particularly for prostatic intraepithelial neoplasia (PIN), the only putative precursor which can be identified according to morphologic criteria. However, it is likely that prostatic adenocarcinoma might arise from precursor lesions other than PIN, although these cannot be recognized with certainty at the present time. In this review, we summarize the current state of knowledge regarding the cell-biological and genetic bases for linking PIN and prostatic adenocarcinoma. It is conceivable that a stem cell of basal phenotype, or an amplifying cell, is the target of prostatic carcinogenesis. Prominent genetic heterogeneity is characteristic of both PIN and carcinoma; and multiple foci of PIN arise independently within the same prostate. This observation suggests that a field effect probably underlies prostatic neoplasia. Multiple foci of cancer also often arise independently, lending additional support to this hypothesis. The strong genetic similarities between PIN and cancer strongly suggest that evolution and clonal expansion of PIN, or other precursor lesions, may account for the multifocal etiology of carcinoma. Uncertainties with respect to identification of those precursor lesions which are most likely to progress to invasive and metastatic prostate cancer reinforce the requirement for objective immunohistochemical or molecular biological markers of the aggressive phenotype.

Adenocarcinoma↗
PubMed2000

Preoperative prediction of surgical margin status in patients with prostate cancer treated by radical prostatectomy.

PURPOSE: We sought to determine the preoperative factors associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer. PATIENTS AND METHODS: The study group consisted of 339 patients who were treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic. None received preoperative adjuvant therapy. The mean age at the time of surgery was 66 years (range, 45 to 79 years). All specimens were totally embedded and whole-mounted. Positive surgical margin was defined as the presence of cancer cells at the inked margins. Numerous pathologic characteristics in needle biopsies and preoperative clinical findings were analyzed. RESULTS: The overall margin positivity rate was 24%. In univariate analysis, preoperative serum prostate-specific antigen (PSA) level, Gleason score, perineural invasion, percentage of cancer in the biopsy specimens, and number and percentage of biopsy cores involved by cancer were all associated with positive surgical margins. In multivariate analysis, preoperative serum PSA level (odds ratio for a doubling of PSA levels, 1.9; 95% confidence interval, 1.5 to 2.4; P <.001) and percentage of cancer in the biopsy specimens (odds ratio for a 10% increase, 1.3; 95% confidence interval, 1.2 to 1.4; P <.001) were predictive of margin status in radical prostatectomy. With use of preoperative serum PSA level and percentage of cancer in the biopsy as predictors of surgical margins, the overall accuracy as measured by the area under the receiver operating characteristic curve was 0.74. CONCLUSION: Preoperative serum PSA level and percentage of cancer in the biopsy specimens were independently associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer. The combination of these two factors provides a high level of predictive accuracy for margin status.

Aged↗
PubMed2000

High expression of somatostatin receptors and messenger ribonucleic acid for its receptor subtypes in organ-confined and locally advanced human prostate cancers.

To evaluate the potential application of somatostatin (SST) analogs as an adjuvant treatment for prostate cancer, we characterized the binding sites for SST octapeptide analogs on prostate cancers in patients treated with radical prostatectomy. The affinity and density of binding sites for SST analog RC-160 on 80 surgical specimens of prostate cancers were determined by ligand competition assays. The expression of messenger ribonucleic acid (mRNA) for SST receptor subtype 1 (SSTR1), subtype 2 (SSTR2), and subtype 5 (SSTR5) was also investigated in 22 samples by RT-PCR. Fifty-two of 80 specimens (65%), showed a single class of specific binding sites for RC-160 with a mean dissociation constant (K(d)) of 9.44 nmol/L and a mean maximal binding capacity of 754.8 fmol/mg membrane protein. The mRNA for SSTR1 was detected in 86% of samples, whereas the incidences of mRNA for SSTR2 and SSTR5 were 14% and 64%, respectively. The expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160 binding. In patients at high risk of cancer recurrence (stage pT3 and/or Gleason score of 8-10), the incidence of RC-160 binding (65.7%) was similar to that observed in the low risk group (64.3%). The demonstration of the high incidence of octapeptide-preferring SSTRs in organ-confined and locally advanced prostate cancers supports the merit of further investigations of the application of SST analogs and their radionuclide and cytotoxic derivatives for adjuvant treatment of patients at high risk of cancer recurrence after radical prostatectomy. Such approaches could be also considered for patients with advanced prostate cancer at the time of relapse.

Aged↗
PubMed2000

Grading and staging of bladder carcinoma in transurethral resection specimens. Correlation with 105 matched cystectomy specimens.

We compared the grading and staging of transurethral resection of the bladder (TURB) and cystectomy specimens for 105 patients who underwent radical cystectomy for urothelial carcinoma between 1980 and 1984. Of 105 patients, 96% underwent cystectomy within 100 days of TURB (median interval, 10 days). Grading was performed according to the 1998 World Health Organization/International Society of Urologic Pathology grading system and staging according to the 1997 TNM classification. Histologic grade was low-grade, 13; high-grade, 92 in TURB specimens; low-grade, 17; high-grade, 88 in cystectomy specimens. Pathologic stage was Ta, 15; T1, 55; and T2, 35 in TURB specimens; Ta, 5; T1, 19; T2, 19; T3, 46; and T4, 16 in cystectomy specimens. Histologic grade at TURB was associated with pathologic stage at cystectomy (P < .001). When all advanced-stage (muscle-invasive) carcinomas (pT2 or more) were considered together, 55 patients were understaged by TURB, 4 had higher stage in TURB than in cystectomy, and 46 were the same stage as by cystectomy. Forty-three of 55 patients with stage T1 carcinoma at TURB had advanced-stage carcinoma at cystectomy, including 34 who had extravesicular extension (pT3 or more). We found pathologic understanding by TURB occurs in a significant number of patients with bladder cancer; the newly proposed grading system predicted final pathologic stage.

Adult↗
PubMed2000

Criteria for biopsy diagnosis of minimal volume prostatic adenocarcinoma: analytic comparison with nondiagnostic but suspicious atypical small acinar proliferation.

CONTEXT: Minimal volume prostatic adenocarcinoma (defined as involving less than 5% of biopsy tissue) is diagnosed increasingly today because of successful cancer screening. We previously described the diagnostic category called atypical small acinar proliferation (ASAP), suspicious for but not diagnostic of malignancy, present in about 2.5% of routine prostatic needle biopsy specimens. OBJECTIVE: To establish the criteria enabling a distinction between ASAP and cancer. DESIGN: We prospectively evaluated clinical and histologic findings from all 319 patients consecutively diagnosed as having ASAP or minimal cancer by prostatic needle biopsy in a consultation service. Seventeen histopathologic features were assessed. RESULTS: Fifty-six patients (18%) had ASAP, and 100 (31%) had minimal cancer; the remaining 163 (51%) had benign diagnoses, high-grade prostatic intraepithelial neoplasia, or larger amounts of cancer. The mean age of patients with ASAP did not differ from that of patients with minimal cancer (64.2 years vs 63.3 years; P =.65). In 10 of 17 histopathologic findings, ASAP differed significantly from minimal cancer. Among architectural findings, ASAP foci averaged 0.4 vs 0.8 mm (P <.0001) and comprised a mean of 11 vs 17 acini (P <.0001). Infiltrative growth occurred in 75% of ASAP foci and 100% of minimal cancers (P <. 0001). Among cytologic findings, ASAP was significantly less likely than cancer to have mitotic figures (0% vs 10%, respectively; P <. 01) or prominent nucleoli in at least 10% of cells (55% vs 100%, respectively; P <.0001) and showed more frequent nuclear hyperchromasia (44% vs 9%, respectively; P <.0001) and less nuclear enlargement (P =.0002). Luminal blue mucin secretions were less common in ASAP than cancer (6% vs 33%, respectively; P <.0001), but eosinophilic granular secretions and crystalloids were about equally frequent. Concomitant high-grade prostatic intraepithelial neoplasia was present in 23% of ASAP cases and 57% of cancers (P <.0001). Moderate-to-severe atrophy confounded 59% of cases with ASAP and 35% of cancers (P =.003); both ASAP foci and cancer were associated with inflammation in about a quarter of cases. In each case with ASAP, we stratified our level of suspicion among 3 categories (favor benign, uncertain, and favor carcinoma). As suspicion increased so did the mean nuclear enlargement and percentage of cases with infiltrative growth and nuclear hyperchromasia (all P <.05). CONCLUSIONS: These criteria, which differ significantly between ASAP and minimal volume cancer, can help to separate patients for whom a second biopsy is recommended from candidates for prostatectomy or other therapy.

Adenocarcinoma↗
PubMed2000

Prognostic factors in prostate cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND: Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in prostate cancer and stratified them into categories reflecting the strength of published evidence and taking into account the expert opinions of the Prostate Working Group members. MATERIALS AND METHODS: Factors were ranked according to the previous College of American Pathologists categorical rankings: category I, factors proven to be of prognostic importance and useful in clinical patient management; category II, factors that have been extensively studied biologically and clinically but whose importance remains to be validated in statistically robust studies; and category III, all other factors not sufficiently studied to demonstrate their prognostic value. Factors in categories I and II were considered with respect to variations in methods of analysis, interpretation of findings, reporting of data, and statistical evaluation. For each factor, detailed recommendations for improvement were made. Recommendations were based on the following aims: (1) increasing uniformity and completeness of pathologic evaluation of tumor specimens, (2) enhancing the quality of data collected pertaining to existing prognostic factors, and (3) improving patient care. RESULTS AND CONCLUSIONS: Factors ranked in category I included preoperative serum prostate-specific antigen level, TNM stage grouping, histologic grade as Gleason score, and surgical margin status. Category II factors included tumor volume, histologic type, and DNA ploidy. Factors in category III included perineural invasion, neuroendocrine differentiation, microvessel density, nuclear roundness, chromatin texture, other karyometric factors, proliferation markers, prostate-specific antigen derivatives, and other factors (oncogenes, tumor suppressor genes, apoptosis genes, etc).

Biomarkers, Tumor↗
PubMed2000

High incidence of receptors for luteinizing hormone-releasing hormone (LHRH) and LHRH receptor gene expression in human prostate cancers.

PURPOSE: Agonistic analogs of luteinizing hormone-releasing hormone (LHRH) are widely used for therapy of advanced prostate cancer based upon their ability to suppress testosterone secretion in patients. Various studies also indicate that LHRH analogs might have direct inhibitory effects on prostate tumors mediated by specific LHRH receptors. In this study we investigated the presence and characteristics of receptors for LHRH and their messenger (m) ribonucleic acid (RNA) expression in specimens of human prostate adenocarcinomas and benign prostatic tissue. MATERIALS AND METHODS: In vitro ligand competition assays as well as reverse transcriptase polymerase chain reaction (RT-PCR) were performed to investigate the expression of receptors for LHRH in surgical specimens of human prostate cancers and benign prostatic tissue. RESULTS: Sixty-nine of 80 (86%) cancers exhibited specific, medium to high-affinity binding for [D-Trp6]LHRH with a dissociation constant (Kd) of 6.55+/-0.4 nM and a maximal binding capacity (Bmax) of 483.6+/-25.4 fmol./mg. membrane protein. Two prostate cancer patients who were treated with the LHRH agonist goserelin prior to prostatectomy did not show tumor LHRH receptors. The expression of mRNA for LHRH receptors was observed in 19 of 22 (86%) prostate cancers. Benign prostatic tissue also displayed LHRH receptor gene expression, but exhibited lower Bmax value. There was a negative correlation (p <0.001) between LHRH receptor binding capacity and cancer grade (Gleason score); higher Gleason scores were associated with significantly lower binding capacity but an increased binding affinity. CONCLUSIONS: The expression of specific receptor proteins for LHRH in human prostate cancer provides a rationale for the improvement in methods for therapy of this malignancy based on LHRH analogs.

Aged↗
PubMed2000

Positive and negative biopsies in the pre-prostate specific antigen and prostate specific antigen eras, 1980 to 1997.

PURPOSE: We assess temporal trends in prostate biopsy incidence, utilization and cancer yield in the community before and after the introduction of serum prostate specific antigen (PSA) to the community medical practice MATERIALS AND METHODS: Study subjects comprised all Olmsted County men with a first prostate biopsy performed between January 1, 1980 and December 31, 1997. Medical records of all study subjects (1,729) were reviewed for clinical information from the first and all subsequent biopsies. RESULTS: Annual age adjusted prostate biopsy incidence increased from 113/100, 000 (95% confidence interval 76, 150) in 1980 to 487/100,000 (421, 554) in 1992 and decreased to 264/100,000 (219, 309) in 1997. For men 50 to 59 years old biopsy incidence increased 400% from 137/100, 000 in 1980 to 1986 to 686/100,000 in 1993 to 1997. Overall, there were 93/100,000 more negative biopsies and 49/100,000 more positive biopsies in 1993 to 1997 than in 1980 to 1986. The overall cancer yield of 36% was essentially unchanged across periods (p = 0.6). However, by age cancer yield decreased from 29% to 21% (1980 to 1986 versus 1993 to 1997) for men 50 to 59 years old but increased from 38% to 45% for those 70 to 79 years old. CONCLUSIONS: Overall cancer yield from prostate biopsies has changed little during the last 15 years. Increased cancer yield for men 70 years old or older has been offset by the decreased yield in younger men. Attention must now be given to diagnostic techniques which might reduce the incidence of negative biopsies and improve cancer yield in younger men.

Aged↗
PubMed2000

Treatment of extraprostatic cancer in clinically organ-confined prostate cancer by permanent interstitial brachytherapy: is extraprostatic seed placement necessary?

PURPOSE: Successful treatment with ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB) relies on effective radiation coverage of intraprostatic and clinically occult extraprostatic cancer. This study examines prostatectomy findings as they relate to treatment of extraprostatic extension (EPE) of cancer and TIPPB techniques and dosimetry. MATERIALS AND METHODS: A total of 313 prostatectomy specimens from patients with clinical tumor classification T1-T2b adenocarcinomas, serum prostate-specific antigen <20 ng/mL, and Gleason score <8 were whole mounted and evaluated for intraprostatic cancer volume and extraprostatic radial distance, area of perforation, and cancer density. From these data, extraprostatic cancer volume is calculated and used to estimate extraprostatic tumor control probabilities using the linear quadratic radiobiological model and Poisson statistics. TIPPB dose-gradient characteristics at the prostate periphery are examined. RESULTS: Intraprostatic cancer volume ranges from 0 to 38 cc, whereas extraprostatic cancer volume ranges from 0 to 4.6 cc (mean 0.06 cc). The radial distance of EPE ranges from 0 to 4.4 mm (mean 0.18 mm). The ratio of extraprostatic to intraprostatic cancer volume ranges from 0% to 18% (mean 0.4%). CONCLUSIONS: Only small amounts of clinically occult extraprostatic cancer were identified in the majority of specimens with EPE. Tumor control probability calculations suggest that this volume of cancer may be treated effectively with TIPPB. Treatment of this cancer possibly is achieved with an intraprostatic implant, but treatment of all cancers identified in this study suggests that some extraprostatic seed placement is desirable.

Adenocarcinoma↗
PubMed2000

Outcome prediction with p53 immunostaining after radical prostatectomy in patients with locally advanced prostate cancer.

PURPOSE: Conventional pathological variables in prostate cancer may not provide optimal prediction of patient outcome. Pathological findings and p53 immunostaining were measured prospectively in radical prostatectomy specimens to determine the incremental improvement in prediction of patient outcome over clinical findings. MATERIALS AND METHODS: From a previous prospective study of 392 consecutive patients with prostate cancer who did not receive preoperative therapy and were treated with radical prostatectomy 25 had pathological stage pT3aN0M0, 24 had pT3bN0M0, 2 had pT2bN1M0, 7 had pT3aN1M0 and 14 had pT3bN1 prostate cancer. These locally advanced stage cases comprise the current study population and further analysis was done with p53 immunostaining. All prostate specimens were totally embedded, serially sectioned and whole mounted. We examined pathological, clinical and laboratory findings as well as p53 immunostaining. RESULTS: Median followup was 5.4 years (range 0.5 to 6.4). Univariate analysis revealed that pathological stage, 10% or greater immunostaining for p53, area and length of extraprostatic cancer extension, and cancer volume (all p </=0.03) were associated with biochemical (prostate specific antigen) or clinical failure. When all variables were considered in stepwise multivariate analysis none attained statistical significance after p53 status entered the model (p <0.01, risk ratio 2.9 for 10% or greater versus less than 10%, 95% confidence interval 1.4-6.2). The concordance index analysis for the predictive ability of prostate specific antigen, stage, grade and ploidy (c = 0.66) was inferior to the predictive ability of a statistical model also including p53 status (c = 0.71). CONCLUSIONS: In cases of locally advanced stage cancer p53 immunoreactivity after radical prostatectomy improves outcome prediction. Addition of this variable to those routinely determined may identify a subset of patients who would benefit from more intensive postoperative surveillance and adjuvant therapy.

Aged↗
PubMed2000

The cell cycle inhibitors p21WAF1 and p27KIP1 are associated with survival in patients treated by salvage prostatectomy after radiation therapy.

We evaluated p27KIP1 and p21WAF1 expression in 52 patients treated by salvage radical prostatectomy and bilateral pelvic lymphadenectomy for biopsy-proven locally persistent or recurrent prostate cancer after external beam radiation therapy. We defined low and high expression based on the median value observed in our sample. Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p21 (< or =5%), compared with 94 and 100%, respectively, for those with high expression of p21 (>5%; P = 0.02 and 0.01, respectively). Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p27 (<50%), compared with 88 and 96%, respectively, for those with high expression of p27 (> or =50%; P = 0.06 and 0.01, respectively). These findings indicate that p21 and p27 expression levels are significant predictors of survival for patients selected for salvage prostatectomy for recurrent prostate cancer.

Aged↗
PubMed2000

Immunohistochemical changes in prostate cancer after androgen deprivation therapy.

Androgen deprivation induces substantial changes in the phenotype of prostate cancer that are accompanied by alterations in protein expression. Immunohistochemical studies allow precise cellular localization of such expression, thereby providing an understanding of the biochemical alterations caused by therapy. Expression of proteins may be increased (e.g., multiple growth factors, heat shock protein), decreased (e.g., microvessel density, proliferation markers, certain integrins), or remain unchanged (e.g., prostate specific antigen, prostatic acid phosphatase, prostate-specific membrane antigen, and other secretory proteins). Variations in immunoreactivity may be of prognostic value in some patients. This report summarizes the existing literature regarding changes in tissue expression of proteins, as determined by immunohistochemistry, and the clinical implications of these changes.

Adenocarcinoma↗