Jaana Hagström

MMP-7 as a prognostic marker in colorectal cancer

Matrix metalloproteinase-7 is capable of degrading many extracellular matrix proteins and cellular adhesions. In many malignancies, it is overexpressed, and it plays a role in cancer progression by enhancing tumor invasion and thereby metastatic potential. The purpose of this study was to evaluate the association between MMP-7 tissue expression and prognosis in colorectal cancer. From 623 patients who underwent surgery for colorectal cancer, surgical specimens were collected into tissue array blocks and stained by immunohistochemistry for MMP-7. Specimens from 545 patients were suitable for analysis. In specimens from 105 patients (19.3%), MMP-7 scored as high; in 103 (18.9%), as moderate; and in 134 (24.9%), as mild. In 203 cases (37.2%), immunoreactivity was negative. A significant correlation appeared between MMP-7 immunoexpression and tumor differentiation. High MMP-7 positivity associated with poor prognosis during a 5-year follow-up. During longer follow-up, the differences in survival between groups disappeared. MMP-7 is a potential target for tumor therapy, which should be evaluated in clinical trials.

MMP-7 overexpression is an independent prognostic marker in gastric cancer

To enable cancer to invade and to metastasize, the surrounding stroma must be degraded. Matrix metalloproteinase-7 (MMP-7) is capable of degrading many extracellular matrix proteins and cellular adhesions, is overexpressed in many malignancies, and plays a role in tumour progression. The purpose of this study was to evaluate the association between MMP-7 tissue expression and patients’ prognosis in gastric cancer. From 264 patients who underwent surgery for gastric cancer, surgical specimens were collected on tissue array blocks and stained by immunohistochemistry for MMP-7. In 27 (10.2%) of the specimens, immunopositivity was found as high, in 50 (18.9%) as moderate and in 51 (19.3%) as weak. In 136 cases (51.5%), the immunopositivity was negative. A statistically significant correlation appeared between high MMP-7 expression and poor survival. In conclusion, our results suggest that MMP-7 expression may prove helpful in evaluating gastric cancer prognosis.

Expression of matrix metalloproteinases-2, -8, -13, -26, and tissue inhibitors of metalloproteinase-1 in human osteosarcoma.

Osteosarcoma (OS) is among most common malignant tumour of bone. Matrix metalloproteinases (MMPs) are predominantly associated with poor prognosis of several cancers, although some of them, like MMP-8, seem to have a protective role in some cancers. We analyzed the distribution patterns of MMP-2, -8, -13, -26, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in 25 OS patients. MMP-2, -8, -13, -26 and TIMP-1 were mostly detected in sarcoma cells. Response to chemotherapy affected the amount of MMP-2, -8, and -13 in resection sections when compared to biopsies: patients with excellent or good response had less positivity to MMP-2 in chemotherapy samples than those with moderate or poor response. We conclude that MMP-2, -8, -13, -26, and TIMP-1 are expressed in OS tissue, and all, except protective MMP-8, were also found in metastases indicating that MMPs and TIMP-1 can participate in the OS progression.

The changing surgical management of juvenile nasopharyngeal angiofibroma

The management of juvenile nasopharyngeal angiofibroma (JNA) has changed during the last decades but it still continues to be a challenge for the multidisciplinary head and neck surgical team. The aim of this study was to review the used treatment approach and outcome of JNA in a single institution series of 27 patients diagnosed and treated during the years 1970–2009. All patients were male, with the median age of 17xa0years (range 11–33xa0years). Surgery was used as the primary treatment in every case. Surgical approaches varied, transpalatal approach (Nxa0=xa014) being the most common approach used in this series. During the last decade various other techniques were applied, including endoscopic (Nxa0=xa03) resection. Two patients were additionally treated with antiangiogenic agents and one patient with stereotactic radiotherapy. The primary recurrence rate was 37% and it seemed to correlate with vascular density of tumour and the surgical approach used. We suggest that the management of JNA should be planned by an experienced head and neck surgeon, as part of a multidisciplinary team, preferably in a tertiary referral setting, and the recent development of the available therapies should be taken into account to minimise the risk of recurrence.

Histopathological findings in parotid gland metastases from renal cell carcinoma

Metastatic tumours involving the parotid gland arising from non-head and neck origin are rare. Immunohistochemistry has improved the differential diagnosis of these lesions. Current immunohistochemical markers allow the distinction between a number of potential primary tumours (e.g., lung, kidney and breast). We present the clinical and histomorphological features of three renal cell carcinoma (RCC) patients presenting with a parotid mass, review the literature of various non-head and neck malignancies metastasizing to the parotid gland, and discuss their differential diagnosis. Two females and one male, aged 58 to 76xa0years, presented with a parotid tumour of renal cell origin. In one case, the parotid mass was the first clinical manifestation. In the two other cases, a nephrectomy had been performed 5–9xa0years earlier because of RCC. The cases showed a highly vascular parotid lesion causing difficulty in interpretation of the fine needle aspirate. Two patients underwent a superficial parotidectomy and one patient an open biopsy of the parotid gland tumour. Immunohistochemical stainings for vimentin, CD10 and PNRA were positive suggesting renal cell origin, which was later confirmed. Clinical and radiological evaluations and diagnosis by fine needle aspiration may prove difficult partly due to the vascular nature of parotid metastasis of renal cell carcinoma. Immunohistochemical staining is useful in identifying the primary tumour.

Tumour-associated trypsin inhibitor TATI is a prognostic marker in colorectal cancer.

Background: The tumour-associated trypsin inhibitor TATI is expressed together with trypsin in many cancer forms, and an elevated serum level associates with poor prognosis. TATI can reduce tissue destruction by inhibiting trypsin and other proteinases, and in some cancer forms, its high tissue expression is associated with favourable prognosis. We analyzed the prognostic values of TATI, trypsinogen-1 and trypsinogen-2 immunoexpression from tissue array blocks constructed from surgical specimens of 592 colorectal cancer patients. Results: TATI positivity correlated negatively with differentiation (p < 0.001) and positively with the histological type of adenocarcinoma (p < 0.001). Trypsinogen-1 and trypsinogen-2 positivity correlated with Dukes’ stage (p = 0.045, p = 0.050); the percentage of trypsinogen-1- and trypsinogen-2-positive tumours was lower in metastasized (Dukes’ stage C–D) than in local (Dukes’ stage A–B) disease. In addition, trypsinogen-2 correlated inversely with differentiation (p = 0.012). In univariate analysis, the expression of TATI associated with more favourable cancer-specific survival (p = 0.010). In multivariate analysis, low TATI (p = 0.044), age (p < 0.001), Dukes’ stage (p < 0.001), tumour differentiation (p = 0.020) and location in the rectum (p = 0.006) were independent prognostic factors for adverse outcome. Furthermore, TATI expression was an independent prognostic factor in a subgroup of trypsinogen-1- (p = 0.007) and trypsinogen-2-positive (p = 0.006) tumours. Conclusion: TATI tissue expression is an independent prognostic marker in colorectal cancer.

Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration

BackgroundTo investigate tear fluid concentration of matrix metalloproteinase 8 (MMP–8) and its relation to conjunctival inflammatory cell infiltration in persistent non—allergic eosinophilic conjunctivitis (NAEC).MethodsTwo groups were included: 26 consecutive adult patients with NAEC (conjunctival eosinophils at least 1+ [1-10 eosinophils/slide], skin prick test [SPT] to common allergens negative), and 26 asymptomatic adult persons (no conjunctival eosinophils, SPT negative). MMP–8 tear fluid concentrations were determined by immunofluorometric assay, and conjunctival brush cytology samples from NAEC patients were used for MMP–8 immunocytochemistry. Gelatin zymography was used to illustrate proteolytic activity within the tear fluid samples.ResultsThe mean MMP–8 concentration was significantly higher among NAEC patients (214.3u2009± 327.7xa0μg/l) than among healthy persons (50.4u2009± 62.3xa0μg/l, Pu2009<u20090.0001). In the NAEC patients, tear fluid MMP–8 correlated with the numbers of conjunctival neutrophils (ru2009=u20090.66, Pu2009=u20090.0002) as well as with goblet cells and columnar epithelial cells (ru2009=u20090.54 for both, Pu2009=u20090.045), but not with the lymphocyte numbers (ru2009=u2009-0.36, Pu2009=u20090.0741). By immunocytology, MMP–8 protein could also be detected in vivo in the inflammatory cell population within the conjunctiva. Zymography revealed that proteolysis was significantly higher in the NAEC group, and activated enzymes were practically found only in the NAEC group.ConclusionsThe results showed that NAEC is an inflammatory condition characterized by increased tear fluid MMP–8 levels, probably derived from both inflammatory and structural conjunctival cells. The increased proteolytic activity in NAEC patients may indicate risk of conjunctival structural changes (remodeling).

The developing management of esthesioneuroblastoma: a single institution experience

Esthesioneuroblastoma remains a challenging disease because of its rarity, the complexity of surrounding structures, missing opinions of optimal treatment protocol, and complications associated with necessary surgery. Our objective was to analyse the management and outcome of a cohort of patients with esthesioneuroblastoma from 1990 to 2009 in a tertiary medical centre. There were 17 eligible patients (8 males and 9 females) with the median age of 53xa0years (range 20–75xa0years). An obvious inconsistency was noted in the management of the various tumours of the present series during the two decades due to a lack of a uniform treatment protocol. The median follow-up time was 57.5xa0months (range 3–158xa0months). Nine patients (seven with curative treatment intent) died of the disease with the median time from diagnosis to death of 60xa0months (range 3–161xa0months). Eight patients had no evidence of the disease at last follow-up visit (median 76xa0months, range 24–119xa0months). Recurrences were documented in seven of the patients. The median time from end of primary treatment to a recurrence was 57xa0months (range 6–110xa0months). The 5-year overall survival and disease-free survival was 68 and 62%, respectively. The management of ENB should be planned by an experienced head and neck surgeon as part of a multidisciplinary team in a tertiary referral setting. Multimodality therapy with long-term follow-up is preferable and should be set based on the available disease-specific classifications for clinical staging and histopathological grading.

Experience of head and neck extracranial schwannomas in a whole population-based single-center patient series

Due to their rarity most of the literature concerning head and neck extracranial schwannomas consists of case reports and small patient series. The aim of the study was to describe population-based incidence, presenting signs and symptoms, management and outcome of head and neck extracranial schwannomas in a larger patient group. All the head and neck extracranial schwannoma patients managed during 1987–2008 at the Helsinki University Central Hospital with a referral area of 1.5 million inhabitants were searched. Altogether 47 patients were identified and subjected to retrospective chart review. Population-based incidence of head and neck extracranial schwannomas was 0.14/100,000/year. Eighty-eight percent of the patients had symptoms, which had lasted on average for 11.5xa0months prior to diagnosis. Presenting signs and symptoms were diverse depending on the affected nerve. Ninety-four percent of the patients were treated surgically. Sixty-four percent of the operations were macroscopically radical. The tumor capsule was intentionally left in place in 9xa0%. Surgery-related complications were detected in only 7xa0% of the patients, but 1xa0month postoperatively 52xa0% of them had symptoms, majority relating to different nerve deficits. Treatment of extracranial head and neck schwannomas remains challenging. The tumor is benign, and it grows slowly in a vast majority of cases, but its symptoms are highly variable. Correct timing of surgery is essential, as also patients who are preoperatively asymptomatic may suffer severe postoperative morbidity. Preoperative patient counseling needs to address the risks of neurological sequelae.

Oral lichen planus and chronic junctional stomatitis: differences in lymphocyte subpopulations

Objective. Oral lichen planus (OLP) is an oral counterpart or oral manifestation of the common skin disease lichen planus. Chronic junctional stomatitis (CJS) is a relatively unknown condition characterized by a stromal lymphocyte infiltrate, which is also a diagnostic feature of OLP. The differential diagnosis of OLP and CJS is unclear and they have been suggested to represent variants of the same disease. Material and methods. To investigate possible differences in lymphocyte (sub)populations between these two conditions, we immunostained 10 OLP and 10 CJS specimens for CD1-a, and the lymphocyte markers, CD3, CD4, CD5, CD8, and CD20. We scored the staining results by a four-step grading system and used the Fisher exact test to analyze them statistically. Results. The proportional amount of (CD20 positive) B lymphocytes was higher in CJS than in OLP and the predominance of CD4 positive T lymphocytes over CD8 positive T lymphocytes was stronger in OLP than in CJS. The differences were statistically significant. Conclusion. The results reflect differences in the lymphatic infiltrate between OLP and CJS. Their significance needs further investigation.