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Elizabeth Montgomery

Publications and source records attributed to Elizabeth Montgomery.

At least 37 records · Page 2Linked to original sources
PubMed2005

Rab11a immunohistochemical analysis does not distinguish indefinite, low-, and high-grade dysplasia in Barrett esophagus.

Our aim was to determine whether p53 and Rab11a immunoreactivity enhance diagnostic assessment of esophageal dysplasia. Histologic sections from 68 cases of Barrett esophagus obtained as part of a 12-institution study were stained with antibodies to p53 and Rab11a, randomized, and coded. The mucosal surface layer and deeper glands were scored blindly on a semiquantitative scale. The correlations between p53 and Rab11a scoring with the consensus diagnosis of dysplasia were analyzed. The histologic scale was as follows: no dysplasia, indefinite, low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma, and invasive carcinoma. Rab11a staining was most prominent in epithelia negative for dysplasia but with regenerative features. There was an inverse relationship between Rab11a staining and findings of surface dysplasia (P < .02, chi(2)). However, statistical significance largely reflected loss of Rab11a immunoreactivity in intramucosal and invasive carcinoma, which was not a diagnostic dilemma. There was a strong positive correlation of p53 immunoreactivity with an increasing degree of epithelial dysplasia and carcinoma (P < .03, chi(2)). Rab11a immunoreactivity did not enhance the diagnostic assessment of dysplasia in Barrett esophagus. The previously reported positive correlation of p53 immunoreactivity with the presence of dysplasia in Barrett esophagus was confirmed.

Adenocarcinoma↗
PubMed2005

Absent or elevated middle ear muscle reflexes in the presence of normal otoacoustic emissions: a universal finding in 136 cases of auditory neuropathy/dys-synchrony.

We extracted a subpopulation of 136 patients (from our database of 257 AN/AD subjects) in whom middle ear muscle reflexes had been measured. None showed normal reflexes at all frequencies tested. Only three subjects showed any reflexes at 95 dB HL or below, but never at both 1 and 2 kHz in both ears whether ipsilaterally or contralaterally elicited. All the other reflex measures in these remaining 133 patients were either absent or observed above 100 dB HL, which is incongruous with their normal otoacoustic emissions throughout the frequency bands. Therefore, we urge colleagues to test ipsilateral middle ear muscle reflex at least at 1 kHz and 2 kHz in any perinatal hearing screening that depends solely on otoacoustic emissions. If the emissions are present and the reflexes are absent or elevated, an ABR may be required to properly intervene, because the management of AN/AD patients often differs drastically from what the behavioral audiogram or the ABR suggest.

Acoustic Impedance Tests↗
PubMed2005

Solitary testicular myofibroma: a case report and review of the literature.

Myofibromas are benign mesenchymal neoplasms of myofibroblastic origin. Most present as solitary lesions at any age, but the presentation of multiple lesions in newborns and infants is known as infantile myofibromatosis. Multicentric lesions commonly involve soft tissues and bone and may involve internal organs, where they are associated with an unfavorable prognosis. Solitary lesions involving the viscera are rare. We report a case of a 3-month-old male infant with a left testicular mass detected during an evaluation for suspected torsion. The patient underwent orchiectomy, revealing a nodular mass with grossly evident foci of necrosis. Histologically, the lesion exhibited small fascicles of plump eosinophilic, smooth muscle actin-positive spindle cells, alternating with larger areas of primitive cells with vesicular nuclei and scant cytoplasm arranged around a hemangiopericytoma-like vasculature. To our knowledge, this is the first report of a myofibroma localized within the testis.

Actins↗
PubMed2005

Is there a way for pathologists to decrease interobserver variability in the diagnosis of dysplasia?

Many obstacles interfere with our efforts to screen patients with Barrett esophagus. Probably the largest is choosing the appropriate patient group for screening. Beyond this problem, sampling error on the part of endoscopists is probably more serious a problem than observer variation among pathologists reviewing patient samples. Pathologists agree well on lesions that merit close follow-up or other intervention (high-grade dysplasia and invasive carcinoma), although interobserver agreement between pathologists interpreting lesser lesions is not good. This lack of agreement is not likely to improve substantially, and many adjunct markers are being sought in an attempt to identify patients with lesions of lower grades that are most likely to progress, allowing doctors to identify patients who would benefit from upgraded surveillance.

Barrett Esophagus↗
PubMed2004

Telomere lengths of translocation-associated and nontranslocation-associated sarcomas differ dramatically.

Sarcomas can be divided into those with specific translocations displaying monotonous cytomorphology, and those with complex karyotypes and marked cellular pleomorphism. Telomeres contain terminal DNA sequence repeats that maintain chromosomal stability. Telomeres shorten with cell division and may become dysfunctional leading to chromosomal instability. Using a fluorescence in situ hybridization/immunofluorescence method to assess telomere lengths in archival tissues we analyzed these two types of sarcomas using paraffin-embedded primary tumor specimens. Tissues from nine sarcomas with characteristic translocations (two synovial sarcomas, two alveolar rhabdomyosarcomas, two desmoplastic round cell tumors, and one each of infantile fibrosarcoma, myxoid liposarcoma, cellular congenital mesoblastic nephroma) and nine without (four malignant fibrous histiocytomas, two leiomyosarcomas, one pleomorphic rhabdomyosarcoma, one dedifferentiated chondrosarcoma, and one malignant peripheral nerve sheath tumor) were analyzed. In all (nine of nine) cases with specific translocations, which generally have few karyotypic abnormalities, telomere lengths were similar to or reduced compared to surrounding nonneoplastic tissues. In contrast, telomeres in cases lacking specific translocations, which generally contain complex karyotypes, were often found to be dramatically lengthened and heterogeneous. In addition to markedly elongated telomeres, seven of nine (78%) complex cases exhibited large brightly stained regions corresponding to a specific type of promyelocytic leukemia nuclear body found in immortalized cells that maintain telomeres in a telomerase-independent manner [alternative lengthening of telomeres (ALT) pathway]. This phenotype is unlike that of epithelial neoplasms that typically display complex karyotypes with abnormally short telomeres maintained by the enzyme telomerase. The discovery of heterogeneous telomere lengths and evidence of the ALT pathway in the majority of sarcomas with complex karyotypes supports the existence of a telomere maintenance pathway incapable of full karyotypic stabilization in pleomorphic sarcomas. These findings provide additional molecular-genetic evidence supporting the dichotomous grouping of sarcomas into those with characteristic signature translocations without extensive additional karyotypic abnormalities, and those without such signature translocations that typically display very complex karyotypes, and point to telomere dysfunction as a plausible contributor to the chromosomal aberrations found in complex sarcomas.

Cell Nucleus↗
PubMed2004

Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature.

Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of OO was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known OO were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO.

Adolescent↗
PubMed2004

CD44 loss in gastric stromal tumors as a prognostic marker.

BACKGROUND: The adhesion molecule CD44 (CD44s; CD44H) and its isoforms (CD44v3-6 and v9) are preferentially expressed by different cell types. These transmembrane glycoproteins are involved in cell-cell and cell-matrix interactions and in cell trafficking and, thus, may play a role in tumor metastasis and/or local invasion. The expression pattern of CD44s and variant isoforms, particularly CD44v6 and CD44v9, of some neoplasms, including soft tissue tumors, correlates with clinical course and outcome. The clinical behavior of gastrointestinal stromal tumors (GIST) is site specific; however, other reliable predictors of clinical outcome have not been identified. Thus, the prognostic value of CD44s and isoform expression in GIST were evaluated by immunohistochemistry of tissue microarrays. DESIGN: Paraffin-embedded formalin-fixed tissue cores (129: 103 GIST and 26 normal stomach smooth muscle) from 33 patients with clinical outcome data were collected and used for the construction of the tissue microarrays. One to five tissue cores from each patient specimen were evaluated (mean = 3 tissue cores/patient). Array slides were stained with anti-CD44s (CD44H) and with antibodies to v3, v4, v5, v6, and v9 isomers. CD44s and isoform expression and staining intensity were scored semiquantitatively without knowledge of patient identity or outcome: 0 = no; 1 = weak; 2 = moderate; 3 = moderate to strong; 4 = strong. The scores of multiple cores from the same GIST were averaged; the nonneoplastic smooth muscle was similarly graded. CD44s and isoform expression and intensity were compared with outcome. RESULTS: The 33 patients with gastric GIST, 0.8 to 30 cm in size, were followed for 1 to 111 months with a median follow-up of 7 months (mean 17.5 months). The overall median survival was 25 months. Nine of the 33 (27%) patients had metastases, 9 (27%) had recurrent disease, and 9 (27%) died of disease (9-111 months; mean 39 months; median 23 months). All 18 patients with GIST CD44s expression > 2+ were alive at last follow-up (1-62 months; median 3.5 months; mean 11 months). More than half (53%) of patients with GIST CD44s expression < or = 2+ died (9-111 months; median 23 months; mean 38 months); the median follow-up of the surviving patients with CD44 expression < or = 2 was 5 months (2-22 months; mean 6.5 months; log rank P = 0.07). The majority of tumors were variably positive CD44v3 and CD44v4, but there was minimal staining (number of cases and/or expression level) with antibodies directed against the v5, v6, and v9 isomers. CONCLUSION: These preliminary results suggest that although gastric GISTs variably express CD44s and variants, only the expression of CD44s correlates with clinical outcome with loss of CD44s positivity correlating with poor clinical outcome.

Adult↗
PubMed2004

Leiomyosarcoma of the kidney: a clinicopathologic study.

Leiomyosarcoma of kidney is a rare lesion for which limited data are available. Cases coded as leiomyosarcoma of the kidney from three institutions were reviewed. These cases comprised 3 men and 7 women, 40 to 75 years of age. Immunohistochemistry was performed where possible and clinical follow-up information was obtained. On immunohistochemical staining, 6 of 6 tumors expressed smooth muscle actin, desmin, calponin, and h-caldesmon, and epithelial membrane antigen was positive in 1 of 5. Tumors were negative for cytokeratin and S-100 protein. Follow-up information was available for 9 patients. Two patients had metastases at diagnosis, four developed metastases, and two had recurrent disease. Five of 9 died of disease. Two patients were alive with no evidence of disease after 19 and 60 months, and 2 patients were alive with disease after 48 months and 56 months. Comparing outcome with tumor grade, the one patient with grade 1 tumor was alive with no evidence of disease; of 5 patients with grade 2 tumor, 2 died of disease, 1 was alive with no evidence of disease, 1 was alive with disease, and 1 was alive with extensive disease; all 3 grade 3 patients died of disease. In summary, the majority of renal leiomyosarcomas are intermediate or high grade with correspondingly poor prognosis.

Adult↗
PubMed2004

Expression of neuropilin-1 in high-grade dysplasia, invasive cancer, and metastases of the human gastrointestinal tract.

Neuropilin-1 (NRP-1) functions as an axonal guidance molecule in the developing nervous system, and recent work has identified NRP-1 up-regulation in several cancers, including neuroblastomas and breast carcinoma. We examined for the first time NRP-1 expression in a large variety of gastrointestinal carcinomas and precursor lesions to determine whether NRP-1 up-regulation correlated with invasive growth in this system. Protein expression and localization of NRP-1 were studied by immunolabeling and semiquantification in >300 dysplastic, invasive, and metastatic lesions of the gastrointestinal tract, and confirmation of NRP-1 protein expression was performed by Western blot analysis on pancreatic cancer cell lines. NRP-1 expression was limited within normal tissues of the gastrointestinal tract, with prominent labeling present only in endothelial cells, pancreatic islet cells, and the most apical colonic epithelium. Invasive cancer of the esophagus, gallbladder, ampulla of Vater, pancreas (endocrine and exocrine), and colon, however, all demonstrated striking NRP-1 expression. NRP-1 was also identified in precursor lesions of gastrointestinal adenocarcinomas, such as Barrett esophagus and colorectal adenomas. Within the spectrum of precursor lesions, a progressive increase in both intensity and area of expression was evident during histologic progression from low-grade to high-grade dysplasia. Notably, the most intense up-regulation of NRP-1 was apparent at or around the point of invasion, with focal expression of NRP-1 at levels equivalent to the invasive cancer (2- to 3-fold increase). Prominent labeling for NRP-1 was apparent in primary invasive cancers, liver metastases, and a subset of lymph node metastases, with a 2- to 3-fold increase of NRP-1 over dysplastic lesions. We conclude that increased expression of NRP-1 occurs in gastrointestinal adenocarcinomas and in a subset of high-grade precursor lesions. This up-regulation appears to parallel invasive behavior and may therefore be used as a potential marker for cancer aggressiveness in this system.

Adenocarcinoma↗
PubMed2004

Serrated colorectal polyps: emerging evidence suggests the need for a reappraisal.

A set of polyps that superficially resemble ordinary hyperplastic polyps of the left colon but with divergent morphology and probably divergent biology has become apparent. Such polyps differ from typical small left-sided hyperplasic polyps by the large sizes they may attain, their tendency to be right-sided, and subtle morphologic differences. It is important to separate these polyps, which some have called "sessile serrated polyps" from hyperplastic polyps as they are associated with progression to carcinoma probably through mismatch repair defects.

Cell Division↗
PubMed2003

Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma.

PURPOSE: We investigated aberrant methylation patterns in esophageal adenocarcinoma and correlated the findings to patient survival and tumor recurrence. EXPERIMENTAL DESIGN: Gene promoter methylation was performed in 82 samples from 41 esophagectomy patients consisting of 41 adenocarcinoma samples, each with its adjacent nonmalignant tissue, which included one sample with Barretts metaplasia. The methylation status of seven genes was determined. Epigenetic silencing was confirmed using immunohistochemical staining. Kaplan-Meier plots were constructed using disease-specific survival as the primary end point and the interval from surgery to tumor recurrence as the secondary end point. The association of clinicopathological and biomolecular risk factors to survival and recurrence was performed using the Log-rank test and Cox proportional hazards model for multivariate analysis. RESULTS: Methylation frequencies of the genes analyzed were APC, 68%; E-cadherin, 66%; O(6)-methylguanine DNA methyltransferase, 56%; ER, 51%; p16, 39%; DAP-kinase, 19%; and TIMP3, 19%. DNA methylation of some genes individually showed only trends toward diminished survival, whereas patients whose tumors had >50% of their gene profile methylated had both significantly poorer survival (P = 0.04) and earlier tumor recurrence (P = 0.05) than those without positive methylation. By multivariate analysis, the hazard ratios (HRs) with positive methylation status were more powerful predictors of survival [HR 2.7 (1.14-6.45; 95% confidence interval)] and tumor recurrence [HR 2.5 (1.11-5.6)] than age (HR 2.03 and 1.96, respectively) or stage (HR 1.48 and 1.67, respectively). CONCLUSIONS: Our data suggest that positive methylation status for multiple genes in esophageal adenocarcinoma is a predictor of poor prognosis.

Adenocarcinoma↗
PubMed2003

Duodenal reflux produces hyperproliferative epithelial esophagitis--a possible precursor to esophageal adenocarcinoma in the rat.

Esophageal reflux of duodenal contents converts a rat nitrosamine esophageal cancer model from squamous cell carcinoma to adenocarcinoma. Further, there was a tendency for male rats to have a higher incidence of cancer than female rats. However, chemical castration with the gonadotropin-releasing hormone analog leuprolide did not protect male or female animals from developing cancer. We have identified an early (6-week) hyperproliferative epithelial cell reaction to duodenal reflux. We carried out experiments to assess the specificity of duodenal reflux in producing the hyperproliferative epithelial precursor lesion. Animals underwent specific surgical procedures to produce esophageal reflux of pure duodenal contents, mixed gastroduodenal, or bland intestinal contents. A hyperproliferative mucosal esophagitis developed in the group with duodenal reflux but not in the other groups. Mucosal thickness in the duodenal reflux group reached seven times that of normal mucosa at 6 weeks. These results suggest that esophageal reflux of duodenal contents plays an important role in the pathogenicity of proliferative esophagitis and the potential development of esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2003

Epithelioid sarcoma: an immunohistochemical analysis evaluating the utility of cytokeratin 5/6 in distinguishing superficial epithelioid sarcoma from spindled squamous cell carcinoma.

BACKGROUND: Epithelioid sarcoma (ES) is a rare, aggressive soft tissue tumor characterized by nodular aggregates of epithelioid and/or spindled cells that are immunoreactive to cytokeratins (CKs) and epithelial membrane antigen. ES that arises in the dermis may cause epidermal ulceration and can resemble, clinically, morphologically and immunohistochemically, cutaneous squamous cell carcinoma. CK 5/6 has recently been found to be an excellent marker of squamous cell carcinoma, including spindled variants, but it is not known if this marker can be utilized to distinguish superficial ES from cutaneous spindled squamous cell carcinoma (SSCC). METHODS: Twenty-four cases of ES with typical histologic features and 10 cases of SSCC with ultrastructural evidence of epithelial differentiation were studied. Immunohistochemical analysis using an antibody to CK 5/6 was performed. The extent of immunoreactivity was evaluated in a semiquantitative manner using the following scale: 0, < 5% of cells staining; 1+, 6-25% of cells staining; 2+, 26-50% of cells staining; 3+, 51-75% of cells staining; 4+, > 75% of cells staining. RESULTS: CK 5/6 was expressed in all 10 cases of SSCC, including one case with 3+ staining and six cases with 4+ staining. In contrast, CK 5/6 staining was found only in rare tumor cells (1+ staining) in one of 24 (4%) cases of ES. CONCLUSIONS: CK 5/6 staining is useful in distinguishing superficial ES from cutaneous SSCC.

Biomarkers, Tumor↗
PubMed2003

Paratesticular liposarcoma: a clinicopathologic study.

Paratesticular liposarcomas are rare and typically reported as isolated cases or as components of larger studies of liposarcomas. We studied a series of these tumors. All cases of paratesticular liposarcomas were retrieved from the archives of the Royal Marsden Hospital and the Johns Hopkins Hospital. Slides were reviewed and clinical information obtained. There were 30 paratesticular liposarcomas from men aged 41-87 years (mean 63 years; median 65 years) that involved the spermatic cord (23, 76%), testicular tunics (6, 20%), and epididymis (1, 4%). Tumors ranged from 3 to 30 cm (mean 11.7 cm; median 10 cm). Nineteen were well-differentiated liposarcomas (WDLs) and 10 were dedifferentiated liposarcomas (DDLs, five with high-grade and five with low-grade dedifferentiation). One was a myxoid/round cell liposarcoma with 70% round cell areas. All patients were treated by radical orchiectomy. One patient with WDL received radiation after his second recurrence and the myxoid/round cell liposarcoma received radiation and chemotherapy. Follow-up information was available for 16 of the patients, including 10 WDLs (range 24-216 months, mean 106 months), 5 DDLs (14-30 months, median 24 months), and for the myxoid/round cell liposarcoma (14 months) (range for all cases 14 months to 22 years; mean 87 months, median 36 months). Six of the WDLs (60%) recurred at 2, 4, 6, 10, 18, and 21 years (median 8 years). The lesion that recurred at 18 years (case no. 6) displayed foci of high-grade dedifferentiation in the recurrence, although the patient was disease free at 19 years. One patient with WDL had two recurrences at 4 and 7 years, and another had six recurrences over a 17-year period. Only one example of DDL recurred, at 30 months; another patient, who refused therapy for 15 years, had a primary tumor 30 cm in diameter, displayed pulmonary metastases 1 month after excision, and died after 14 months. The patient with MRCL had abdominal metastases after 1 year and was alive at 14 months. In summary, paratesticular WDL had a prolonged course with recurrences in more than half the cases, sometimes late. There were no metastases and the overall prognosis was good. One DDL recurred and only one of five (20%) developed metastases, but the mean follow-up for DDL was only 24 months.

Adult↗
PubMed2003

Analysis of protein expression and gene mutation of c-kit in colorectal neuroendocrine carcinomas.

Primary neuroendocrine carcinomas of the colon are rare but highly aggressive malignancies. The recent observations that c-kit protooncogene, a tyrosine kinase, is overexpressed in a subset of small cell lung cancer and that selective kinase inhibitors block the in vitro growth of small cell lung cancer cell lines prompted us to investigate the expression and mutation status of the c-kit gene in colorectal neuroendocrine carcinomas. Sixty-six cases of primary colorectal neuroendocrine carcinoma were collected from 13 institutions, including 36 small cell carcinomas and 30 moderately differentiated neuroendocrine carcinomas. Immunohistochemical studies using a polyclonal antibody against c-kit protein (CD117) demonstrated a strong and diffuse cytoplasmic staining in 15 cases (23%), which were relatively equally distributed in the small cell and moderately differentiated subgroups. As controls, 25 conventional colorectal adenocarcinomas, 26 colorectal adenomas and 19 colorectal carcinoid tumors were all negative, whereas 15 gastrointestinal stromal tumors were all positive, for kit expression. In contrast to gastrointestinal stromal tumors, kit-overexpressing neuroendocrine carcinomas showed no mutations in the juxtamembrane domain (exon 11) of the c-kit gene as determined by mutational analysis. Kaplan-Meier analysis with the log-rank test revealed that the patients with kit-positive tumors did not differ significantly in survival from those with kit-negative tumors (P = 0.77). These results indicate that c-kit overexpression observed in a subset of colorectal neuroendocrine carcinomas may not be mediated via activating mutations, and does not appear to be an initiating event during tumorigenesis because of lack of c-kit expression in other types of colorectal epithelial neoplasms. More importantly, our observations may have potential therapeutic implications since specific tyrosine kinase inhibitors have shown promise in the management of patients with kit-expressing malignancies.

Adult↗
PubMed2003

Loss of Stk11/Lkb1 expression in pancreatic and biliary neoplasms.

We have documented previously somatic mutations of STK11/LKB11, the gene responsible for Peutz-Jeghers syndrome (PJS), in a small proportion of sporadic pancreatic adenocarcinomas, intraductal papillary mucinous neoplasms (IPMNs), and biliary adenocarcinomas. In this report, we characterize the expression of Stk11, the protein product of the STK11 gene, in a larger series of pancreatic and biliary neoplasms. First, the specificity of the Stk11 antibody was established in 23 neoplasms (22 IPMNs and 1 biliary adenocarcinoma) with known STK11 gene status. Complete absence of labeling was seen in the neoplastic cells of 3 of the 3 (100%) cases with previously documented biallelic inactivation of the STK11 gene, whereas 16 of the 20 (80%) IPMNs, presumably with at least one wild-type STK11 gene, retained Stk11 expression in the neoplastic cells. The marked decrease or absence of Stk11 expression in four neoplasms with wild-type STK11 suggests that additional mechanisms may account for the lack of Stk11 expression. Subsequently, to further evaluate Stk11 expression in pancreatic and biliary neoplasms, tissue microarrays (TMAs) were constructed from a series of nearly 100 ductal adenocarcinomas and biliary neoplasms. Stk11 expression was lost in 4 of the 56 (7%) pancreatic adenocarcinomas and 1 of the 38 (2.6%) biliary cancers by immunohistochemistry; the absence of labeling was confirmed by repeated immunohistochemical labeling of complete tissue sections for the same cases. Thus, Stk11 expression is abrogated in a small proportion of pancreatic and biliary neoplasms. The inactivation of Stk11 in 27% (6/22) of IPMNs versus 7% (4/56) of pancreatic adenocarcinomas suggests genetic disparities in the pathogenesis of these closely related neoplasms. Immunohistochemical analysis for Stk11 expression may be a valid surrogate for genetic analysis of STK11 gene mutations in cancers.

Adenocarcinoma↗