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Purification and characterization of androgen receptor from steer seminal vesicle.

The androgen receptor has been purified from steer seminal vesicle cytosol by a combination of differential DNA-Sepharose 4B chromatography and testosterone 17 beta-hemisuccinyl-3,3'-diaminodipropylamine-Sepharose 4B affinity chromatography. The procedure produced about 3 micrograms of receptor protein from 35 g of steer seminal vesicle, with a yield of 48%. The receptor protein, as a complex with unlabeled testosterone, was purified approximately 540000-fold. A single band, migrating at 60000 daltons, was observed following electrophoresis on a polyacrylamide gel containing sodium dodecyl sulfate (NaDoDSO4). This was confirmed by affinity labeling of the partially purified receptor with both 17-hydroxy-17 alpha-[3H]methyl-4,9,11-estratrien-3-one and 17 beta-hydroxy-[1,2,4,5,6,7,16,17-3H8)-5 alpha-androstan-3-one 17-(2-bromoacetate), which showed a peak of radioactivity migrating at 60000 daltons by NaDoDSO4 gel electrophoresis. The receptor had an estimated Stokes radius of 35 A and a sedimentation coefficient of 3.8 S in the presence of 0.3 M NaCl. The calculated molecular weight and frictional ratio for the androgen binding activity were 57000 and 1.42, respectively. Chromatofocusing of the purified receptor protein revealed an isoelectric point of 6.6. [3H]Methyltrienolone, bound to the purified receptor, was displaced with methyl-trienolone greater than testosterone greater than 5 alpha-dihydrotestosterone much greater than 3 beta-hydroxy-delta 5-androsten-17-one much greater than 5 alpha-androstane-3 alpha,17 beta-diol. The physicochemical properties of the purified receptor were similar to those of the receptor in crude cytosol. These results demonstrate that the androgen receptor from steer seminal vesicle was substantially purified without significant modification of its physicochemical or steroid binding properties.

Affinity Labels↗

Similarity of vasopressin receptors in seminal vesicles and renal medulla of pigs.

To test the hypothesis that the vasopressin receptors found in seminal vesicles are similar to those present in the renal tubules competition experiments were performed with vasopressin and several analogues with different specificities for the V1 and V2 subtypes of vasopressin receptor. Autoradiographic studies were carried out on sections from seminal vesicles and kidney to identify the cellular target of vasopressin. Vasopressin receptors in renal medulla and seminal vesicles of pigs shared the same rank order of potency for vasopressin and its analogues and were localized in the epithelium of the seminal vesicles and in collecting tubules of renal medulla. These results strongly suggest that the vasopressin receptors present in kidney and seminal vesicles belong to the same subtype, V2, of vasopressin receptor.

Animals↗

Proliferative response of seminal vesicle cells to androgen in mice castrated neonatally and pretreated with estrogen or androgen at adulthood.

Seminal vesicle cells of neonatally castrated adult mice show poor response to androgen, compared to those of mice castrated at adulthood; effects of pretreatment with androgen or estrogen at adulthood on androgen-induced proliferation of the seminal vesicle cells were examined in neonatally castrated mice. Male mice castrated at day 0 after birth were pretreated with daily injections of testosterone propionate (TP, 100 micrograms/mouse), 17 beta-estradiol (E2, 5 micrograms/mouse) or vehicle for 20 days starting from day 60; daily TP injections (100 micrograms/mouse) for 30 days were started again from day 110 in all the pretreated mice to examine androgen-induced proliferation by incorporation of 5-[125I]iodo-2'-deoxyuridine into the whole seminal vesicles. Both TP and E2 pretreatments significantly increased the seminal vesicle weight found before TP treatment. However, androgen-induced proliferation of the seminal vesicle found in neonatally castrated mice (poor response; long duration with a low peak on day 3) was changed at least in part to that found in mice castrated at adulthood (good response; short duration with a high peak on day 3) only following the TP pretreatment but not at all following the E2 pretreatment. The E2 pretreatment induced poor androgen-induced proliferation with a low peak on day 7.

Age Factors↗

Vasopressin receptors in human seminal vesicles: identification, pharmacologic characterization, and comparison with the vasopressin receptors present in the human kidney.

Because of the presence of a high density of vasopressin receptors in the epithelial cells of porcine seminal vesicles similar to the V2 vasopressin receptors of renal tubules, human seminal vesicles and kidney were investigated using quantitative binding and adenylate cyclase studies. Tissues were obtained at surgery from 17 patients with urologic diseases. A homogeneous class of vasopressin binding sites have been found in both seminal vesicles and renal medulla. However, the vasopressin receptors present in these tissues are different in terms of ligand specificity and adenylate cyclase activation. In seminal vesicles, the V1 vasopressin antagonist d(CH2)5 TyrMeAVP is 36-fold, more potent than the V2 agonist dVDAVP in displacing [3H]AVP binding, while in the medullopapillary portion of kidney dVDAVP is 24-fold, more selective than d(CH2)5 TyrMeAVP for the arginine vasopressin binding site. Furthermore, arginine vasopressin induces a dose-dependent increase in adenylate cyclase activity in renal membranes, while it was ineffective in seminal vesicle membranes. These results indicate that a very high affinity (0.2 nM), low capacity (14 fmoles/mg protein) class of vasopressin receptors is present in human seminal vesicles, having pharmacologic characteristics similar to the V1 subtype of vasopressin receptors. The presence of a high affinity (1.6 nM), high capacity (350 fmoles/mg protein) V2 subtype of vasopressin receptors in human renal membranes is also confirmed. The density of the vasopressin receptors present in human seminal vesicles is inversely correlated with patient age, consistent with a physiologic role for vasopressin in the regulation of accessory sex gland activity.

Adenylyl Cyclases↗

Rat seminal-vesicle secretory protein SVS II binds DNA with a preference for the 5' regulatory region of secretory protein SVS IV gene: co-isolation with components of the nuclear matrix.

In rats, the ventral prostate and seminal vesicles produce distinct sets of proteins whose functions and tissue-specific regulation by androgens remain unclear. We have utilized the genes encoding the major secretory protein of seminal vesicles, SVS IV, and the C3 subunit of prostatein of the ventral prostate to study how the nuclear matrix might determine their tissue-specific gene expression. Nuclear matrix proteins were prepared from purified nuclei with DNase and 2 M NaCl, separated in SDS gels, and transferred onto membranes for DNA-binding (southwestern) and immunological (western) analyses. The 5' region of the SVS IV gene (SVS IV-7S) bound to a 45,000-kDa molecular-weight protein band in the nuclear matrix of seminal vesicles but not to that of ventral prostate, kidney, or liver. Sequencing revealed that this band was a seminal-vesicle secretory protein, SVS II, whose identity was confirmed with an anti-SVS II antiserum in western blots. Actin-like protein, similar in mobility to SVS II, was detected in seminal-vesicle and ventral prostate nuclear matrix, but not in seminal-vesicle fluid. Reducing agent (10 mM dithiothreitol) and acidic (pH 6.5) buffer did not eliminate SVS II, but isolation of nuclear matrices with ammonium sulfate, nucleases, and urea decreased SVS II immunoreactivity and removed actin-like protein. SVS II binding to SVS IV-7S DNA was greater than its binding to either a comparable fragment of the C3 gene or linearized pUC-19 plasmid, and it was not eliminated by a 100-fold competition. When seminal-vesicle fluid was mixed with rat liver, some SVS II co-isolated with the nuclear-matrix proteins, indicating that nonspecific interactions contribute to its association with the nucleoskeleton. However, these interactions may not represent the intracellular behavior of SVS II in seminal-vesicle epithelium. Sequence comparisons indicate significant homologies between SVS II and some other seminal proteins, including bovine caltrin, which, under the name seminalplasmin, is known to possess antimicrobial activity. Collectively, these data suggest that in addition to its known functions, SVS II may also bind extraneous DNA in seminal fluid. Additionally, SVS II may participate as a structural component in the organization of a tissue-specific seminal-vesicle nuclear matrix.

Animals↗

Observations on the structure and autonomic innervation of the guinea-pig seminal vesicle and ductus deferens.

A combination of light microscopic, neurohistochemical and electron microscopic techniques were used to study the distribution of autonomic nerves in the seminal vesicle, and in the submucosa of the ductus deferens, in the guinea-pig. In routine histological preparations, the muscle coat of the seminal vesicle consisted largely of circularly orientated smooth muscle cells with an additional longitudinal layer confined to its urethral end. Using fluorescence microscopy, a rich plexus of noradrenergic nerves was demonstrated throughout the muscle coat of the seminal vesicle and this was confirmed electron microscopically. Numerous noradrenergic terminal regions were frequently observed 10-100 nm from adjacent smooth muscle cells, and catecholamine-containing nerve cell bodies were observed in the adventitia of the urethral end of the seminal vesicle. With the light microscope, a rich plexus of AChE+ve nerves was found in the circular muscle layer but the outer longitudinal layer contained few similar nerves. AChE+ve ganglion cells were confined to the adventitia of the urethral end of the seminal vesicle. Electron microscopy revealed a second type of terminal region containing small agranular vesicles, the distribution of which corresponded to that of the AChE+ve nerves observed by light microscopy. In both layers, these terminal regions were associated with other axons, although the circular muscle layer also contained single axons of this type in close association with adjacent smooth muscle cells. Very few noradrenergic nerves were found in the submucosa of the seminal vesicle and ductus deferens and those which were observed usually accompanied the vascular supply. In contrast, a rich AChE+ve nerve network was observed in the submucosa of both the seminal vesicle and the ductus deferens. Electron microscopy revealed numerous groups of submucosal axons, many of which appeared varicose and contained small, agranular vesicles. Similar intra-epithelial axons were occasionally observed in both organs. These findings have been discussed in relation to the possible functional significance of this extensive autonomic innervation.

Animals↗

The major basic proteins of bull seminal vesicle secretion.

We have employed HPLC on reversed phase columns to analyse the major basic proteins from bull seminal vesicle secretion. The identification of proteins was achieved by comparison with authentic protein samples from bull seminal plasma as well as immunological characterisation using antisera directed against the latter proteins. The major basic proteins from bull seminal plasma: bull seminal proteinase inhibitor II (BUSI II), the seminal ribonuclease BS1, the protein P6 as well as the antimicrobial protein were also identified as the main constituents of the fraction of basic proteins derived from seminal vesicle secretion. FPLC using Mono S HR columns was also found to resolve the mixture of basic proteins and proved to be especially useful with respect to the isolation of the antimicrobial protein from basic proteins of seminal vesicle secretion. The identity of the antimicrobial protein from bull seminal plasma with the respective protein from seminal vesicle secretion was confirmed by amino-acid analysis and comparison of tryptic peptide patterns by HPLC. The antimicrobial protein was isolated from seminal vesicle secretion with a yield of 3 mg/ml of secretion.

Amino Acids↗

Effects of the high K+/Na+ deficient solution on mechanical response and wet weight of tissue in vas deferens and seminal vesicle in guinea-pig.

In the present experiments, we investigated contractions of guinea-pig vas deferens or seminal vesicle in various kinds of high K+ solution. The vas deferens showed a phasic contraction followed by a tonic one in hyperosmotic 65 mM KCl (hyper-65K+), isosmotic 60 mM or 120 mM KCl solution. However, isosmotic 154 mM KCl (iso-154K+) solution induced a large phasic contraction followed by a gradual relaxation. Applications of the high K+ solutions to the preparation of seminal vesicle showed almost similar results in tension to those of the vas deferens. In the vas deferens or seminal vesicle, an application of hyper-65K+ solution significantly decreased the relative value for the wet weight of the tissue at 120 min, but that of iso-154K+ solution did not affect the wet weight of both the muscles. In the vas deferens, an hyperosmotic addition of sucrose at a concentration of 25 to 100 mM slightly prevented the tension decreased by the iso-154K+ solution and slightly decreased the relative wet weight. In the seminal vesicle, increasing sucrose concentration significantly increased the tension, but decreased the relative wet weight. In both the muscles of vas deferens and seminal vesicle, an addition of pyrvate or oxalacetate (5.5 mM) to the iso-154K+ solution without glucose maintained the muscle tension at a maximal level in the iso-154K+ solution with glucose for 120 min. Further, the tension decrease in both the muscles induced by iso-154K+ solution was also prevented by hyperosmotic application of NaCl. From these results, it is suggested that the tension decrease by high K+, Na+-deficient solution in the vas deferens is mainly caused by an inhibition of glucose utilization by Na+-deficiency in the medium, however, the seminal vesicle is probably due to the cell swelling and partly the inhibition of glucose utilization by it.

Animals↗

Seminal vesicle biopsies in the preoperative staging of prostatic cancer.

Twenty-five patients with localized prostate cancer underwent seminal vesicle biopsies before radical prostatectomy. A transrectal probe of 7 MHz, a 18-gauge needle and a biopsy gun were used. The preoperative biopsy established the absence of seminal vesicle invasion in 89% of cases. When the seminal vesicles are positive at biopsy, capsular penetration is observed in 100% of the cases and lymph node positivity in 50%. When seminal vesicles are negative at biopsy and the prostate-specific antigen level is less than 20 ng/ml (n less than 2.5), capsular penetration of greater than 1 cm is absent in 100% of cases and lymph nodes are positive in only 7% of cases. Biopsy of the seminal vesicle, as an outpatient procedure, improves the preoperative staging of prostate cancer before radical prostatectomy: negative biopsies are good predictors of the absence of lymph node invasion.

Antigens, Neoplasm↗

High incidence and histogenesis of seminal vesicle adenocarcinoma and lower incidence of prostate carcinomas in the Lobund-Wistar prostate cancer rat model using N-nitrosomethylurea and testosterone.

The origin of chemically induced male accessory sex gland tumors was studied in Lobund-Wistar rats. Rats were treated at the age of 3 months with a single intravenous injection of 30 mg N-nitrosomethylurea (NMU)/kg body weight and given subcutaneous silastic implants filled with 40 mg testosterone propionate. Previous reports described a high incidence of prostate carcinomas in these rats with this treatment protocol. Additional animal groups included untreated controls, rats that received only an injection of 30 mg NMU/kg, and rats that were subjected to ablation of the seminal vesicle lobes prior to the treatment with NMU and testosterone. Three to 14 rats per group were sacrificed 4 to 10 months after NMU treatment and all remaining rats after 12 months. Twenty-four additional rats died or became moribund during the study. All rats were necropsied and the dorsolateral and ventral prostate and seminal vesicles with coagulating gland (anterior prostate) were examined histologically according to a standardized protocol. Lesions detected included atypical hyperplasia in all glands (resembling prostate intraepithelial neoplasia of human beings), adenomas in seminal vesicles only, and early carcinomas and adenocarcinomas in seminal vesicles and coagulating gland. Early carcinomas of the seminal vesicle, microscopically small and with invasion of the lamina propria and/or tunica muscularis, were detected as rapidly as 4 months after treatment. The vast majority (> 95%) of the grossly visible nodules/masses originated from the seminal vesicles. Testosterone treatment enhanced occurrence and increased the incidence of all lesions, particularly of seminal vesicle adenocarcinomas, from 30% (7/23) to 64% (21/33). Coagulating gland tumors were found in 21% (7/33) of the rats. Ablation of the seminal vesicle lobes reduced the incidence of seminal vesicle adenocarcinomas to 11% (3/29), and these tumors arose from tissues remaining within the parenchyma of the seminal vesicle/prostate complex after ablation. Thus, NMU-induced and testosterone-promoted male sex gland tumors of the Lobund-Wistar rat arise almost exclusively in the seminal vesicles and coagulating gland (anterior prostate), are highly invasive in seminal vesicles before attaining a grossly visible size, and progress rapidly within 4 months, spreading to adjacent tissues and other organs.

Adenocarcinoma↗

Isolation and culture of rat seminal vesicle epithelial cells. The use of the secretory protein SVS IV as a functional probe.

A method for the isolation and culture of seminal vesicle epithelial cells obtained from control and androgen-primed sexually-immature, uncastrated rats is described. This method allows the establishment of monolayer cultures from aggregates of seminal vesicle epithelial cells isolated after trypsin and collagenase digestion. Phase contrast and transmission electron microscopic methods demonstrate that cell aggregates, after attaching to the substrate, establish within 48 h a colony-like, epithelial-like growth pattern. Immunofluorescent localization studies of SVS IV, an androgen-dependent secretory protein purified from rat seminal vesicle secretion, show that cultured seminal vesicle epithelial cells are immunoreactive. An electrophoretic analysis of [35S]methionine-labeled secretory proteins immunoprecipitated with rabbit anti-SVS IV serum demonstrate that, whereas SVS IV is newly-synthesized and accumulated in the medium of cultured seminal vesicle cells established from androgen primed rats, cultured cells from control rats appear to synthesize and accumulate SVS IV in a precursor form. Results of this work show that seminal vesicle epithelial cells in culture not only retain several structural features representative of the tissue but also serve as a potential system for the study of androgen action.

Animals↗

Seminal vesicle amyloidosis: morphological, histochemical and immunohistochemical observations.

Subepithelial deposits of amyloid were detected within the seminal vesicles of 13 males from a total of 143 unselected autopsies (9%). The incidence increased with increasing age. The amyloid was classified using histochemistry, immunohistochemistry and clinical features. Eight cases were categorized as senile vesicle amyloid, two as systemic AA amyloid with secondary involvement of the seminal vesicle, and three as mixed amyloidosis. The morphological appearances of the different categories of seminal vesicle amyloidosis are similar but a different distribution is common. The staining characteristics of senile vesicle amyloid suggest that this is a different amyloid protein, perhaps locally derived within the seminal vesicle.

Adult↗

Hydatid disease of the seminal vesicle: a rare presentation of hydatid cyst.

Seminal vesicle belongs to the unusual sites of the hydatid cyst presentation. Even though the patient had a history of surgically treated hydatid disease of the liver, however, solitary echinococcal cyst of the seminal vesicle is a rare condition. Surgical removal of the cyst intact is the treatment of choice.

Adult↗

Prognosis of seminal vesicle involvement by transitional cell carcinoma of the bladder.

PURPOSE: Transitional cell carcinoma (TCC) of the bladder that extends directly into contiguous organs (pT4) portends a poor prognosis. The 2002 American Joint Committee on Cancer staging system does not include seminal vesicle involvement by primary TCC of the bladder. In this analysis we evaluated the clinical outcomes and prognostic significance of seminal vesicle involvement with TCC of the bladder after radical cystectomy. MATERIALS AND METHODS: From 1971 to 2001, 1,682 patients underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer. Only those tumors that involved adjacent organs through the bladder wall (pT4) were included. Overall 132 male patients with a median age of 68 years (range 36 to 98) qualified for analysis. Patients were stratified into 4 subgroups of 1) direct extravesical prostatic stromal involvement only in 37 patients (28%), 2) prostatic stroma and seminal vesicle involvement in 37 patients (28%), 3) seminal vesicle involvement only in 10 patients (8%) and 4) other contiguous pelvic organ involvement (stage pT4b) in 48 patients (36%). Overall 88 patients (67%) received some form of adjuvant therapy. At a median followup of 12.5 years (range 0 to 15.2) clinical outcomes were analyzed including overall and recurrence-free survival using Kaplan-Meier plots. RESULTS: There was no significant difference in clinical outcomes or prognosis for groups 2 and 3, thus they were combined for analysis. Five-year overall survival for any seminal vesicle involvement (10%) was significantly worse than prostatic stromal involvement only (38%) but was similar to pT4b tumors (7%, p <0.0001). The 5-year recurrence-free survival for seminal vesicle involvement (14%) was also significantly worse than prostatic stromal involvement alone (68%) but similar to that pT4b disease (25%, p = 0.01). Results were controlled for lymph node status. CONCLUSIONS: Patients with extravesical tumor extension into seminal vesicles and contiguous pelvic organs are at high risk for recurrence and progression. Involvement of the seminal vesicles by direct extension of bladder TCC portends a prognosis similar to that of pT4b disease and should, therefore, be classified as such.

Adult↗

Flow cytometric determination of ploidy in prostatic adenocarcinoma: a comparison with seminal vesicle involvement and histopathological grading as a predictor of clinical recurrence.

Flow cytometry was used to evaluate 88 deparaffinized radical prostatectomy specimens to compare deoxyribonucleic acid ploidy in prostatic adenocarcinoma as a predictor of disease progression with other well documented predictors of clinical recurrence. Aneuploidy, Gleason grade and seminal vesicle involvement were nonindependent variables, and all correlated to statistical significance with disease recurrence. The incidence of aneuploidy in the total population was 51 of 88 (58 per cent). Aneuploidy was found in 25 of 28 primary tumors (89 per cent) from patients who subsequently had recurrent disease. Aneuploidy was noted in 40 of 59 specimens (68 per cent) exhibiting seminal vesicle involvement, compared to 11 of 29 (38 per cent) without seminal vesicle involvement (p less than 0.01). The probability of an interval free of disease of 60 months was calculated by Kaplan-Meier analysis to be 85 per cent in diploid specimens compared to 9 per cent in aneuploid specimens (p less than 0.001), and 87 per cent in the absence of seminal vesicle involvement compared to 28 per cent in the presence of seminal vesicle involvement (p less than 0.003). The probability of remaining free of disease in patients exhibiting concomitant diploidy and seminal vesicle involvement (17) was 73 per cent compared to 8 per cent in those with aneuploid specimens and seminal vesicle involvement (p less than 0.004). The incidence of recurrence in patients with Gleason sums of 7 or less was 22 per cent compared to 62 per cent in patients with Gleason sums of greater than 7. There was a 29 per cent incidence of recurrence in intermediate grade tumors (Gleason sum 5 to 7) but only 5 per cent of the patients with intermediate grade diploid tumors had recurrent disease. In conclusion, the recognition of a deoxyribonucleic acid aneuploid stem line in a primary prostatic adenocarcinoma is correlated statistically with a greater likelihood of seminal vesicle invasion and subsequent development of recurrent disease. The markedly increased probability of remaining free of disease in diploid patients, even in the presence of seminal vesicle involvement, suggests that routine flow cytometric analysis in prostatic adenocarcinoma would significantly enhance prognostic stratification.

Adenocarcinoma↗

Seminal vesicle cyst associated with ipsilateral renal agenesis.

Seminal vesicle cysts present at the age of high sexual activity. They manifest with symptoms of bladder irritation and pain on ejaculation. They arise because of congenital obstruction of ejaculatory duct. Diagnosis can be made by careful rectal examination supplemented by an intravenous urogram, cystogram, seminal vesiculogram, and cystourethroscopy. Surgical excision of the cyst is the definitive treatment. We present a case of right seminal vesicle cyst associated with ipsilateral renal agenesis, with a review of the pertinent literature.

Adult↗

Immunological relationships between specific sperm proteins and secretory polypeptides from seminal vesicles.

Rat and bovine testicular and posttesticular spermatozoa, in situ or removed from the seminal pathways were studied for the presence and the binding of seminal vesicle secretory proteins. A protein cross-reactive with an antibody against rat seminal secretory sulfhydryloxidase was found in mitochondria of pachytene primary spermatocytes which are sequestered during spermiogenesis and collected in the residual bodies of late spermatids. This indicates the replacement of one generation of mitochondria by another during spermiogenesis. Using an antibody against the SVS II polypeptide from rat seminal vesicles, an intrinsic immunoreactive protein was detected in the principal piece of the sperm tail as well as an extrinsic protein (presumably secreted by the epididymis) on the sperm head. The actin-capping capacity of SVS II indicates the functional relation of this immunoreactive membrane protein with actin or an actinrelated protein. Ampullary bovine spermatozoa, contrary to their epididymal precursors contain immunoreactive major protein, secreted from bull seminal vesicles, firmly incorporated into the (sub) plasmalemmal protein in the middle piece. In this case, a secretory protein from seminal vesicles is incorporated into the sperm proteins. This is presumably an important process, related with the initiation of hypermotility of spermatozoa.

Animals↗

The mechanisms and prognostic significance of seminal vesicle involvement by prostate cancer.

To assess the mechanisms and prognostic significance of seminal vesicle involvement (SVI) by prostatic adenocarcinoma, we analyzed 312 radical prostatectomy specimens obtained from patients with T1-T3 prostate cancer. Detailed pathological examination demonstrated three patterns of SVI. Type I involvement was direct spread along the ejaculatory duct complex into the seminal vesicles. Type II involvement was spread outside of the prostate, through the capsule, and then into the seminal vesicle. Type III involvement was characterized by the finding of isolated deposits of cancer in the seminal vesicle with no contiguous primary cancer in the prostate. We found SVI in 64 patients (21%), who have been followed for a mean of 31 months (range 1-101). A defining criterion for progression was clinically apparent local or distant recurrence or a postoperative serum prostate specific antigen (PSA) > or = 0.4 ng/ml (Hybritech). Type I SVI was found in 17 (26%), Type II in 21 (33%), and Type III in 8 (13%) cases. In 18 patients (28%), the pattern of SVI appeared to be a combination of types I and II (categorized as Type I+II). Type III (isolated metastasis) SVI was associated with significantly smaller cancers (median, 3.13 vs. 6.7 cc; p < 0.0005) and fewer positive margins (0 vs. 32%; p = 0.05) than in other types. Type II SVI, with direct extension through the capsule, was associated with a significantly higher risk of lymph node metastasis (8 vs. 33%; p < 0.05). When patients with lymph node metastases were excluded, there was a trend toward a more favorable prognosis (p = 0.09) for patients with type III SVI than with other types. Overall, patients with type III SVI had a progression-free survival rate similar to that of 83 patients with extracapsular extension without SVI. We conclude that the prognostic significance of SVI may not be uniformly ominous; instead, it may depend on the specific mechanism of involvement and the pathologic features of the primary tumor.

Adenocarcinoma↗